@article{lisee_evans-pickett_davis-wilson_munsch_longobardi_schwartz_lalush_franz_pietrosimone_2023, title={Delayed cartilage oligomeric matrix protein response to loading is associated with femoral cartilage composition post-ACLR}, ISSN={["1439-6327"]}, DOI={10.1007/s00421-023-05253-w}, abstractNote={[[{:Label=>"PURPOSE", :NlmCategory=>"OBJECTIVE"}, "To determine associations between immediate and delayed response of serum cartilage oligomeric matrix protein (sCOMP) to loading (i.e., 3000 walking steps) and femoral cartilage interlimb T1ρ relaxation times in individual's post-anterior cruciate ligament reconstruction (ACLR)."], [{:Label=>"METHODS", :NlmCategory=>"METHODS"}, "This cross-sectional study included 20 individuals 6-12 months following primary ACLR (65% female, 20.5 ± 4.0 years old, 24.9 ± 3.0 kg/m", {:sup=>"2"}, ", 7.3 ± 1.5 months post-ACLR). Serum samples were collected prior to, immediately following, and 3.5 h following walking 3000 steps on a treadmill at habitual walking speed. sCOMP concentrations were processed using enzyme-linked immunosorbent assays. Immediate and delayed absolute sCOMP responses to loading were evaluated immediately and 3.5 h post-walking, respectively. Participants underwent bilateral magnetic resonance imaging with T1ρ sequences to calculate resting femoral cartilage interlimb T1ρ relaxation time ratios between limbs (i.e., ACLR/Uninjured limb). Linear regression models were fitted to determine associations between sCOMP response to loading and femoral cartilage T1ρ outcomes controlling for pre-loading sCOMP concentrations."], [{:Label=>"RESULTS", :NlmCategory=>"RESULTS"}, "Greater increases in delayed sCOMP response to loading were associated with greater lateral (∆R", {:sup=>"2"}, " = 0.29, p = 0.02) but not medial (∆R", {:sup=>"2"}, " < 0.01, p = 0.99) femoral cartilage interlimb T1ρ ratios. Associations between immediate sCOMP response to loading with femoral cartilage interlimb T1ρ ratios were weak and non-significant (∆R", {:sup=>"2"}, " range = 0.02-0.09, p range = 0.21-0.58)."], [{:Label=>"CONCLUSION", :NlmCategory=>"CONCLUSIONS"}, "Greater delayed sCOMP response to loading, a biomarker of cartilage breakdown, is associated with worse lateral femoral cartilage composition in the ACLR limb compared to the uninjured limb. Delayed sCOMP response to loading may be a more indicative metabolic indicator linked to deleterious changes in composition than immediate sCOMP response."]]}, journal={EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY}, author={Lisee, Caroline and Evans-Pickett, Alyssa and Davis-Wilson, Hope and Munsch, Amanda E. and Longobardi, Lara and Schwartz, Todd A. and Lalush, David and Franz, Jason R. and Pietrosimone, Brian}, year={2023}, month={Jun} }
 @article{phillips_walsh_zurcher_lalush_kinard_tseng_cernasov_kan_cummings_kelley_et al._2023, title={Striatal dopamine in anhedonia: A simultaneous [11C]raclopride positron emission tomography and functional magnetic resonance imaging investigation}, volume={333}, ISSN={["1872-7506"]}, DOI={10.1016/j.pscychresns.2023.111660}, abstractNote={Anhedonia is hypothesized to be associated with blunted mesocorticolimbic dopamine (DA) functioning in samples with major depressive disorder. The purpose of this study was to examine linkages between striatal DA, reward circuitry functioning, anhedonia, and, in an exploratory fashion, self-reported stress, in a transdiagnostic anhedonic sample.Participants with (n = 25) and without (n = 12) clinically impairing anhedonia completed a reward-processing task during simultaneous positron emission tomography and magnetic resonance (PET-MR) imaging with [11C]raclopride, a DA D2/D3 receptor antagonist that selectively binds to striatal DA receptors.Relative to controls, the anhedonia group exhibited decreased task-related DA release in the left putamen, caudate, and nucleus accumbens and right putamen and pallidum. There were no group differences in task-related brain activation (fMRI) during reward processing after correcting for multiple comparisons. General functional connectivity (GFC) findings revealed blunted fMRI connectivity between PET-derived striatal seeds and target regions in the anhedonia group. Associations were identified between anhedonia severity and the magnitude of task-related DA release to rewards in the left putamen, but not mesocorticolimbic GFC.Results provide evidence for reduced striatal DA functioning during reward processing and blunted mesocorticolimbic network functional connectivity in a transdiagnostic sample with clinically significant anhedonia.}, journal={PSYCHIATRY RESEARCH-NEUROIMAGING}, author={Phillips, Rachel D. and Walsh, Erin C. and Zurcher, Nicole R. and Lalush, David S. and Kinard, Jessica L. and Tseng, Chieh-En and Cernasov, Paul M. and Kan, Delia and Cummings, Kaitlin and Kelley, Lisalynn and et al.}, year={2023}, month={Aug} }
 @article{boling_dupell_pfeiffer_wallace_lalush_spang_nissman_pietrosimone_2022, title={In Vivo Compositional Changes in the Articular Cartilage of the Patellofemoral Joint Following Anterior Cruciate Ligament Reconstruction}, ISSN={["2151-4658"]}, DOI={10.1002/acr.24561}, abstractNote={To compare T1ρ relaxation times of the medial and lateral regions of the patella and femoral trochlea at 6 and 12 months following anterior cruciate ligament reconstruction (ACLR) on the ACLR and contralateral extremity. Greater T1ρ relaxation times are associated with a lower proteoglycan density of articular cartilage.}, journal={ARTHRITIS CARE & RESEARCH}, author={Boling, Michelle C. and Dupell, Matthew and Pfeiffer, Steven J. and Wallace, Kyle and Lalush, David and Spang, Jeffrey T. and Nissman, Daniel and Pietrosimone, Brian}, year={2022}, month={Apr} }
 @article{bjornsen_schwartz_lisee_blackburn_lalush_nissman_spang_pietrosimone_2022, title={Loading during Midstance of Gait Is Associated with Magnetic Resonance Imaging of Cartilage Composition Following Anterior Cruciate Ligament Reconstruction}, volume={13}, ISSN={["1947-6043"]}, DOI={10.1177/19476035211072220}, abstractNote={Objective A complex association exists between aberrant gait biomechanics and posttraumatic knee osteoarthritis (PTOA) development. Previous research has primarily focused on the link between peak loading during the loading phase of stance and joint tissue changes following anterior cruciate ligament reconstruction (ACLR). However, the associations between loading and cartilage composition at other portions of stance, including midstance and late stance, is unclear. The objective of this study was to explore associations between vertical ground reaction force (vGRF) at each 1% increment of stance phase and tibiofemoral articular cartilage magnetic resonance imaging (MRI) T1ρ relaxation times following ACLR. Design Twenty-three individuals (47.82% female, 22.1 ±4.1 years old) with unilateral ACLR participated in a gait assessment and T1ρ MRI collection at 12.25 ± 0.61 months post-ACLR. T1ρ relaxation times were calculated for the articular cartilage of the weightbearing medial and lateral femoral (MFC, LFC) and tibial (MTC, LTC) condyles. Separate bivariate, Pearson product moment correlation coefficients (r) were used to estimate strength of associations between T1ρ MRI relaxation times in the medial and lateral tibiofemoral articular cartilage with vGRF across the entire stance phase. Results Greater vGRF during midstance (46%-56% of stance phase) was associated with greater T1ρ MRI relaxation times in the MFC (r ranging between 0.43 and 0.46). Conclusions Biomechanical gait profiles that include greater vGRF during midstance are associated with MRI estimates of lesser proteoglycan density in the MFC. Inability to unload the ACLR limb during midstance may be linked to joint tissue changes associated with PTOA development.}, number={1}, journal={CARTILAGE}, author={Bjornsen, Elizabeth and Schwartz, Todd A. and Lisee, Caroline and Blackburn, Troy and Lalush, David and Nissman, Daniel and Spang, Jeffrey and Pietrosimone, Brian}, year={2022}, month={Jan} }
 @article{evans-pickett_lisee_horton_lalush_nissman_blackburn_spang_pietrosimone_2022, title={Worse Tibiofemoral Cartilage Composition Is Associated with Insufficient Gait Kinetics After ACL Reconstruction}, volume={54}, ISSN={["1530-0315"]}, DOI={10.1249/MSS.0000000000002969}, abstractNote={ABSTRACT Purpose Greater articular cartilage T1ρ magnetic resonance imaging relaxation times indicate less proteoglycan density and are linked to posttraumatic osteoarthritis development after anterior cruciate ligament reconstruction (ACLR). Although changes in T1ρ relaxation times are associated with gait biomechanics, it is unclear if excessive or insufficient knee joint loading is linked to greater T1ρ relaxation times 12 months post-ACLR. The purpose of this study was to compare external knee adduction (KAM) and flexion (KFM) moments in individuals after ACLR with high versus low tibiofemoral T1ρ relaxation profiles and uninjured controls. Methods Gait biomechanics were collected in 26 uninjured controls (50% females; age, 22 ± 4 yr; body mass index, 23.9 ± 2.8 kg·m−2) and 26 individuals after ACLR (50% females; age, 22 ± 4 yr; body mass index, 24.2 ± 3.5 kg·m−2) at 6 and 12 months post-ACLR. ACLR-T1ρHigh (n = 9) and ACLR-T1ρLow (n = 17) groups were created based on 12-month post-ACLR T1ρ relaxation times using a k-means cluster analysis. Functional analyses of variance were used to compare KAM and KFM. Results ACLR-T1ρHigh exhibited lesser KAM than ACLR-T1ρLow and uninjured controls 6 months post-ACLR. ACLR-T1ρLow exhibited greater KAM than uninjured controls 6 and 12 months post-ACLR. KAM increased in ACLR-T1ρHigh and decreased in ACLR-T1ρLow between 6 and 12 months, both groups becoming more similar to uninjured controls. There were scant differences in KFM between ACLR-T1ρHigh and ACLR-T1ρLow 6 or 12 months post-ACLR, but both groups demonstrated lesser KFM compared with uninjured controls. Conclusions Associations between worse T1ρ profiles and increases in KAM may be driven by the normalization of KAM in individuals who initially exhibit insufficient KAM 6 months post-ACLR.}, number={10}, journal={MEDICINE & SCIENCE IN SPORTS & EXERCISE}, author={Evans-Pickett, Alyssa and Lisee, Caroline and Horton, W. Zachary and Lalush, David and Nissman, Daniel and Blackburn, J. Troy and Spang, Jeffrey T. and Pietrosimone, Brian}, year={2022}, month={Oct}, pages={1771–1781} }
 @article{zurcher_walsh_phillips_cernasov_tseng_dharanikota_smith_li_kinard_bizzell_et al._2021, title={A simultaneous [C-11]raclopride positron emission tomography and functional magnetic resonance imaging investigation of striatal dopamine binding in autism}, volume={11}, ISSN={["2158-3188"]}, DOI={10.1038/s41398-020-01170-0}, abstractNote={Abstract The social motivation hypothesis of autism posits that autism spectrum disorder (ASD) is characterized by impaired motivation to seek out social experience early in life that interferes with the development of social functioning. This framework suggests that impaired mesolimbic dopamine function underlies compromised responses to social rewards in ASD. Although this hypothesis is supported by functional magnetic resonance imaging (fMRI) studies, no molecular imaging study has evaluated striatal dopamine functioning in response to rewards in ASD. Here, we examined striatal functioning during monetary incentive processing in ASD and controls using simultaneous positron emission tomography (PET) and fMRI. Using a bolus + infusion protocol with the D2/D3 dopamine receptor antagonist [ 11 C]raclopride, voxel-wise binding potential (BP ND ) was compared between groups (controls = 12, ASD = 10) in the striatum. Striatal clusters showing significant between-group BP ND differences were used as seeds in whole-brain fMRI general functional connectivity analyses. Relative to controls, the ASD group demonstrated decreased phasic dopamine release to incentives in the bilateral putamen and left caudate, as well as increased functional connectivity between a PET-derived right putamen seed and the precuneus and insula. Within the ASD group, decreased phasic dopamine release in the putamen was related to poorer theory-of-mind skills. Our findings that ASD is characterized by impaired striatal phasic dopamine release to incentives provide support for the social motivation hypothesis of autism. PET-fMRI may be a suitable tool to evaluate novel ASD therapeutics targeting the striatal dopamine system.}, number={1}, journal={TRANSLATIONAL PSYCHIATRY}, author={Zurcher, Nicole R. and Walsh, Erin C. and Phillips, Rachel D. and Cernasov, Paul M. and Tseng, Chieh-En J. and Dharanikota, Ayarah and Smith, Eric and Li, Zibo and Kinard, Jessica L. and Bizzell, Joshua C. and et al.}, year={2021}, month={Jan} }
 @article{pfeiffer_spang_nissman_lalush_wallace_harkey_pietrosimone_padua_blackburn_pietrosimone_2021, title={Association of Jump-Landing Biomechanics With Tibiofemoral Articular Cartilage Composition 12 Months After ACL Reconstruction}, volume={9}, ISSN={["2325-9671"]}, DOI={10.1177/23259671211016424}, abstractNote={Background: Excessively high joint loading during dynamic movements may negatively influence articular cartilage health and contribute to the development of posttraumatic osteoarthritis after anterior cruciate ligament reconstruction (ACLR). Little is known regarding the link between aberrant jump-landing biomechanics and articular cartilage health after ACLR. Purpose/Hypothesis: The purpose of this study was to determine the associations between jump-landing biomechanics and tibiofemoral articular cartilage composition measured using T1ρ magnetic resonance imaging (MRI) relaxation times 12 months postoperatively. We hypothesized that individuals who demonstrate alterations in jump-landing biomechanics, commonly observed after ACLR, would have longer T1ρ MRI relaxation times (longer T1ρ relaxation times associated with less proteoglycan density). Study Design: Cross-sectional study; Level of evidence, 3. Methods: A total of 27 individuals with unilateral ACLR participated in this cross-sectional study. Jump-landing biomechanics (peak vertical ground-reaction force [vGRF], peak internal knee extension moment [KEM], peak internal knee adduction moment [KAM]) and T1ρ MRI were collected 12 months postoperatively. Mean T1ρ relaxation times for the entire weightbearing medial femoral condyle, lateral femoral condyle (global LFC), medial tibial condyle, and lateral tibial condyle (global LTC) were calculated bilaterally. Global regions of interest were further subsectioned into posterior, central, and anterior regions of interest. All T1ρ relaxation times in the ACLR limb were normalized to the uninjured contralateral limb. Linear regressions were used to determine associations between T1ρ relaxation times and biomechanics after accounting for meniscal/chondral injury. Results: Lower ACLR limb KEM was associated with longer T1ρ relaxation times for the global LTC (ΔR 2 = 0.24; P = .02), posterior LTC (ΔR 2 = 0.21; P = .03), and anterior LTC (ΔR 2 = 0.18; P = .04). Greater ACLR limb peak vGRF was associated with longer T1ρ relaxation times for the global LFC (ΔR 2 = 0.20; P = .02) and central LFC (ΔR 2 = 0.15; P = .05). Peak KAM was not associated with T1ρ outcomes. Conclusion: At 12 months postoperatively, lower peak KEM and greater peak vGRF during jump landing were related to longer T1ρ relaxation times, suggesting worse articular cartilage composition.}, number={7}, journal={ORTHOPAEDIC JOURNAL OF SPORTS MEDICINE}, author={Pfeiffer, Steven J. and Spang, Jeffrey T. and Nissman, Daniel and Lalush, David and Wallace, Kyle and Harkey, Matthew S. and Pietrosimone, Laura S. and Padua, Darin and Blackburn, Troy and Pietrosimone, Brian}, year={2021}, month={Jul} }
 @article{lisee_spang_loeser_longobardi_lalush_nissman_schwartz_hu_pietrosimone_2021, title={Tibiofemoral articular cartilage composition differs based on serum biochemical profiles following anterior cruciate ligament reconstruction}, volume={29}, ISSN={["1522-9653"]}, DOI={10.1016/j.joca.2021.09.005}, abstractNote={Biochemical joint changes contribute to posttraumatic osteoarthritis (PTOA) development following anterior cruciate ligament reconstruction (ACLR). The purpose of this longitudinal cohort study was to compare tibiofemoral cartilage composition between ACLR patients with different serum biochemical profiles. We hypothesized that profiles of increased inflammation (monocyte chemoattractant protein-1 [MCP-1]), type-II collagen turnover (type-II collagen breakdown [C2C]:synthesis [CPII]), matrix degradation (matrix metalloproteinase-3 [MMP-3] and cartilage oligomeric matrix protein [COMP]) preoperatively to 6-months post-ACLR would be associated with greater tibiofemoral cartilage T1ρ relaxation times 12-months post-ACLR.Serum was collected from 24 patients (46% female, 22.1 ± 4.2 years old, 24.0 ± 2.6 kg/m2 body mass index [BMI]) preoperatively (6.4 ± 3.6 days post injury) and 6-months post-ACLR. T1ρ Magnetic Resonance Imaging (MRI) was collected for medial and lateral tibiofemoral articular cartilage at 12-months post-ACLR. A k-means cluster analysis was used to identify profiles based on biomarker changes over time and T1ρ relaxation times were compared between cluster groups controlling for sex, age, BMI, concomitant injury (either meniscal or chondral pathology), and Marx Score.One cluster exhibited increases in MCP-1 and COMP while the other demonstrated decreases in MCP-1 and COMP preoperatively to 6-months post-ACLR. The cluster group with increases in MCP-1 and COMP demonstrated greater lateral tibial (adjusted mean difference = 3.88, 95% confidence intervals [1.97-5.78]) and femoral (adjusted mean difference = 12.71, 95% confidence intervals [0.41-23.81]) T1ρ relaxation times.Profiles of increased serum levels of inflammation and matrix degradation markers preoperatively to 6-months post-ACLR are associated with MRI changes consistent with lesser lateral tibiofemoral cartilage proteoglycan density 12-months post-ACLR.}, number={12}, journal={OSTEOARTHRITIS AND CARTILAGE}, author={Lisee, C. and Spang, J. T. and Loeser, R. and Longobardi, L. and Lalush, D. and Nissman, D. and Schwartz, T. and Hu, D. and Pietrosimone, B.}, year={2021}, month={Dec}, pages={1732–1740} }
 @article{wang_zhou_yu_wang_zu_lalush_lin_wu_zhou_shen_2019, title={3D Auto-Context-Based Locality Adaptive Multi-Modality GANs for PET Synthesis}, volume={38}, ISSN={["1558-254X"]}, DOI={10.1109/TMI.2018.2884053}, abstractNote={Positron emission tomography (PET) has been substantially used recently. To minimize the potential health risk caused by the tracer radiation inherent to PET scans, it is of great interest to synthesize the high-quality PET image from the low-dose one to reduce the radiation exposure. In this paper, we propose a 3D auto-context-based locality adaptive multi-modality generative adversarial networks model (LA-GANs) to synthesize the high-quality FDG PET image from the low-dose one with the accompanying MRI images that provide anatomical information. Our work has four contributions. First, different from the traditional methods that treat each image modality as an input channel and apply the same kernel to convolve the whole image, we argue that the contributions of different modalities could vary at different image locations, and therefore a unified kernel for a whole image is not optimal. To address this issue, we propose a locality adaptive strategy for multi-modality fusion. Second, we utilize $1 \times 1 \times 1$ kernel to learn this locality adaptive fusion so that the number of additional parameters incurred by our method is kept minimum. Third, the proposed locality adaptive fusion mechanism is learned jointly with the PET image synthesis in a 3D conditional GANs model, which generates high-quality PET images by employing large-sized image patches and hierarchical features. Fourth, we apply the auto-context strategy to our scheme and propose an auto-context LA-GANs model to further refine the quality of synthesized images. Experimental results show that our method outperforms the traditional multi-modality fusion methods used in deep networks, as well as the state-of-the-art PET estimation approaches.}, number={6}, journal={IEEE TRANSACTIONS ON MEDICAL IMAGING}, author={Wang, Yan and Zhou, Luping and Yu, Biting and Wang, Lei and Zu, Chen and Lalush, David S. and Lin, Weili and Wu, Xi and Zhou, Jiliu and Shen, Dinggang}, year={2019}, month={Jun}, pages={1328–1339} }
 @article{pfeiffer_spang_nissman_lalush_wallace_harkey_pietrosimone_schmitz_blackburn_pietrosimone_2019, title={ASSOCIATIONS BETWEEN LATERAL COMPARTMENT T1RHO MRI INTER-LIMB RATIOS AND CHANGES IN WALKING GAIT KINEMATICS FOLLOWING ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION}, volume={27}, ISSN={["1522-9653"]}, DOI={10.1016/j.joca.2019.02.201}, abstractNote={Purpose: Following an anterior cruciate ligament (ACL) injury and reconstruction (ACLR), individuals are at a heightened risk for developing posttraumatic knee osteoarthritis (PTOA). Decreased proteoglycan density of the articular cartilage is an early compositional change associated with early development of PTOA. T1ρ magnetic resonance imaging (MRI) relaxation times are sensitive to interactions between water and macromolecules, such as proteoglycans, within the extracellular cartilage matrix. Greater T1ρ relaxation times are associated with lesser proteoglycan density, which may negatively impact the capacity of the cartilage to resist compressive forces. Furthermore, individuals with an ACLR often demonstrate a “stiffened” or more flexed knee through the stance phase of gait, which may also influence the ability to attenuate forces at the knee. While the relationship between kinematic and kinetic variables during walking and T1ρ MRI relaxation times for the medial femoral and tibial condyles post-ACLR has been examined, the association between kinematic variables and T1ρ MRI relaxation times for the lateral femoral and tibial condyles is not well understood. The lateral femoral (LFC) and tibial (LTC) condyles commonly sustain a traumatic bone contusion during ACL injury, which may predispose the lateral compartment to early changes in cartilage composition. Therefore, the purpose of this study was to examine the associations between changes in walking gait kinematics (peak knee flexion angle [KFA], knee flexion excursion [KFE]) from 6 to 12 months post-ACLR and T1ρ inter-limb relaxation time ratios (ILR) at 12 months post-ACLR. Methods: Twenty-four individuals (50% female, 21.9 ± 3.6 years old, 23.6 ± 2.4 kg/m2) with a unilateral ACLR were prospectively enrolled. T1ρ MRI was acquired at a 12-month post-ACLR follow-up. Five trials of walking gait at self-selected speed were performed at 6 and 12 months post-ACLR. Peak KFA and KFE were extracted from the first 50% of the stance phase of gait in both limbs. Percent change scores for KFA and KFE for both limbs were calculated. T1ρ relaxation times were collected bilaterally on either a Siemens Magnetom TIM Trio 3 Tesla scanner using a 4-channel Siemens large flex coil or a Siemens Magnetom Prisma 3T PowerPack scanner with a XR 80/200 gradient coil at 12 months post-ACLR. A T1ρ prepared 3D FLASH sequence with 500 Hz spin lock power and five spin lock durations (40, 30, 20,10, 0 ms) was used. Mean T1ρ ILR for the entire (Global) weight bearing LFC and LTC were calculated (ILR = ACLR limb / Uninjured limb). The Global-LFC and LTC were further divided into three regions of interest (ROI) corresponding to cartilage overlaying the anterior meniscus, between the meniscal horns (central), and the posterior meniscus. T1ρ ILR at 12 months post-ACLR were calculated for each ROI of the LFC and LTC. Separate, stepwise linear regressions were used to determine associations between peak KFA and KFE and T1ρ ILR after accounting for walking speed and meniscal and/or chondral injury in the lateral compartment (P≤0.05). Results: A decrease in KFE in the injured limb from 6 to 12 months post-ACLR significantly associated with greater T1ρ ILR for Global-LTC (ΔR2=.20, β=-.46, P=.02) as well as the Posterior-LTC (ΔR2=.21, β=-.47, P=.02) and Central-LTC ROI (ΔR2=.24, β=-.51, P=.01) 12 months post-ACLR. Similarly, a decrease in KFE in the uninjured limb from 6 to 12 months post-ACLR significantly associated with greater T1ρ ILR for Global-LFC (ΔR2=.19, β=-.45, P=.03) as well as the Posterior-LFC (ΔR2=.43, β=-.69, P=.01) 12 months post-ACLR. A decrease in peak KFA in the injured limb from 6 to 12 months post-ACLR significantly associated with greater T1ρ ILR for the Central-LFC (ΔR2=.21, β=-.47, P=.04), as well as the Global-LTC (ΔR2=.17, β=-.43, P=.04) and the Central-LTC (ΔR2=.24, β=-.51, P=.01) 12 months post-ACLR. Similarly, a decrease in peak KFA in the uninjured limb from 6 to 12 months post-ACLR significantly associated with greater T1ρ ILR for the Central-LFC (ΔR2=.28, β=-.55, P=.01) 12 months post-ACLR. Conclusions: Decreases in peak KFA for the injured limb and KFE for both limbs from 6 to 12 months post-ACLR associate with greater T1ρ ILR in the lateral tibiofemoral compartment at 12 months post-ACLR. These data suggest individuals who adopt a stiffened knee strategy early post-ACLR may also exhibit changes in cartilage composition. Decreases in knee joint kinematics during walking may reduce an individual’s ability to attenuate force at the knee. This may lead to altered loads distributed through the lateral tibiofemoral joint, which may relate to potential deleterious compositional changes to the articular cartilage. Future work should investigate if using novel rehabilitation techniques to increase peak KFA and KFE during walking post-ACLR influences compositional changes in cartilage of the lateral tibiofemoral compartment.}, journal={OSTEOARTHRITIS AND CARTILAGE}, author={Pfeiffer, S. J. and Spang, J. T. and Nissman, D. and Lalush, D. and Wallace, K. and Harkey, M. S. and Pietrosimone, L. and Schmitz, R. J. and Blackburn, T. and Pietrosimone, B.}, year={2019}, month={Apr}, pages={S136–S137} }
 @article{pfeiffer_spang_nissman_lalush_wallace_harkey_pietrosimone_schmitz_schwartz_blackburn_et al._2019, title={Gait Mechanics and T1 rho MRI of Tibiofemoral Cartilage 6 Months after ACL Reconstruction}, volume={51}, ISSN={["1530-0315"]}, DOI={10.1249/MSS.0000000000001834}, abstractNote={Purpose Aberrant walking biomechanics after anterior cruciate ligament reconstruction (ACLR) are hypothesized to be associated with deleterious changes in knee cartilage. T1&rgr; magnetic resonance imaging (MRI) is sensitive to decreased proteoglycan density of cartilage. Our purpose was to determine associations between T1&rgr; MRI interlimb ratios (ILR) and walking biomechanics 6 months after ACLR. Methods Walking biomechanics (peak vertical ground reaction force (vGRF), vGRF loading rate, knee extension moment, knee abduction moment) were extracted from the first 50% of stance phase in 29 individuals with unilateral ACLR. T1&rgr; MRI ILR (ACLR limb/uninjured limb) was calculated for regions of interest in both medial and lateral femoral (LFC) and medial and lateral tibial condyles. Separate, stepwise linear regressions were used to determine associations between biomechanical outcomes and T1&rgr; MRI ILR after accounting for walking speed and meniscal/chondral injury (P ⩽ 0.05). Results Lesser peak vGRF in the ACLR limb was associated with greater T1&rgr; MRI ILR for the LFC (posterior &Dgr;R2 = 0.14, P = 0.05; central &Dgr;R2 = 0.15, P = 0.05) and medial femoral condyle (central &Dgr;R2 = 0.24, P = 0.01). Lesser peak vGRF loading rate in the ACLR limb (&Dgr;R2 = 0.21, P = 0.02) and the uninjured limb (&Dgr;R2 = 0.27, P = 0.01) was associated with greater T1&rgr; MRI ILR for the anterior LFC. Lesser knee abduction moment for the injured limb was associated with greater T1&rgr; MRI ILR for the anterior LFC (&Dgr;R2 = 0.16, P = 0.04) as well as the posterior medial tibial condyle (&Dgr;R2 = 0.13, P = 0.04). Conclusion Associations between outcomes related to lesser mechanical loading during walking and greater T1&rgr; MRI ILR were found 6 months after ACLR. Although preliminary, our results suggest that underloading of the ACLR limb at 6 months after ACLR may be associated with lesser proteoglycan density in the ACLR limb compared with the uninjured limb.}, number={4}, journal={MEDICINE & SCIENCE IN SPORTS & EXERCISE}, author={Pfeiffer, Steven J. and Spang, Jeffrey and Nissman, Daniel and Lalush, David and Wallace, Kyle and Harkey, Matthew S. and Pietrosimone, Laura S. and Schmitz, Randy and Schwartz, Todd and Blackburn, Troy and et al.}, year={2019}, month={Apr}, pages={630–639} }
 @article{pietrosimone_pfeiffer_harkey_wallace_hunt_blackburn_schmitz_lalush_nissman_spang_2019, title={Quadriceps weakness associates with greater T1 rho relaxation time in the medial femoral articular cartilage 6months following anterior cruciate ligament reconstruction}, volume={27}, ISSN={["1433-7347"]}, DOI={10.1007/s00167-018-5290-y}, abstractNote={[[{:Label=>"PURPOSE", :NlmCategory=>"OBJECTIVE"}, "Quadriceps weakness following anterior cruciate ligament reconstruction (ACLR) is linked to decreased patient-reported function, altered lower extremity biomechanics and tibiofemoral joint space narrowing. It remains unknown if quadriceps weakness is associated with early deleterious changes to femoral cartilage composition that are suggestive of posttraumatic osteoarthritis development. The purpose of the cross-sectional study was to determine if quadriceps strength was associated with T1ρ relaxation times, a marker of proteoglycan density, of the articular cartilage in the medial and lateral femoral condyles 6 months following ACLR. It is hypothesized that individuals with weaker quadriceps would demonstrate lesser proteoglycan density."], [{:Label=>"METHODS", :NlmCategory=>"METHODS"}, "Twenty-seven individuals (15 females, 12 males) with a patellar tendon autograft ACLR underwent isometric quadriceps strength assessments in 90°of knee flexion during a 6-month follow-up exam. Magnetic resonance images (MRI) were collected bilaterally and voxel by voxel T1ρ relaxation times were calculated using a five-image sequence and a monoexponential equation. Following image registration, the articular cartilage for the weight-bearing surfaces of the medial and lateral femoral condyles (MFC and LFC) were manually segmented and further sub-sectioned into posterior, central and anterior regions of interest (ROI) based on the corresponding meniscal anatomy viewed in the sagittal plane. Univariate linear regression models were used to determine the association between quadriceps strength and T1ρ relaxation times in the entire weight-bearing MFC and LFC, as well as the ROI in each respective limb."], [{:Label=>"RESULTS", :NlmCategory=>"RESULTS"}, "Lesser quadriceps strength was significantly associated with greater T1ρ relaxation times in the entire weight-bearing MFC (R", {:sup=>"2"}, " = 0.14, P = 0.05) and the anterior-MFC ROI (R", {:sup=>"2"}, " = 0.22, P = 0.02) of the ACLR limb. A post hoc analysis found lesser strength and greater T1ρ relaxation times were significantly associated in a subsection of participants (n = 18) without a concomitant medial tibiofemoral compartment meniscal or chondral injury in the entire weight-bearing MFC, as well as anterior-MFC and central-MFC ROI of the ACLR and uninjured limb."], [{:Label=>"CONCLUSIONS", :NlmCategory=>"CONCLUSIONS"}, "The association between weaker quadriceps and greater T1ρ relaxation times in the MFC suggests deficits in lower extremity muscle strength may be related to cartilage composition as early as 6 months following ACLR. Maximizing quadriceps strength in the first 6 months following ACLR may be critical for promoting cartilage health early following ACLR."], [{:Label=>"LEVEL OF EVIDENCE", :NlmCategory=>"METHODS"}, "Prognostic level 1."]]}, number={8}, journal={KNEE SURGERY SPORTS TRAUMATOLOGY ARTHROSCOPY}, author={Pietrosimone, Brian and Pfeiffer, Steven J. and Harkey, Matthew S. and Wallace, Kyle and Hunt, Christian and Blackburn, J. Troy and Schmitz, Randy and Lalush, David and Nissman, Daniel and Spang, Jeffrey T.}, year={2019}, month={Aug}, pages={2632–2642} }
 @article{wang_yu_wang_zu_lalush_lin_wu_zhou_shen_zhou_2018, title={3D conditional generative adversarial networks for high-quality PET image estimation at low dose}, volume={174}, ISSN={["1095-9572"]}, DOI={10.1016/j.neuroimage.2018.03.045}, abstractNote={Positron emission tomography (PET) is a widely used imaging modality, providing insight into both the biochemical and physiological processes of human body. Usually, a full dose radioactive tracer is required to obtain high-quality PET images for clinical needs. This inevitably raises concerns about potential health hazards. On the other hand, dose reduction may cause the increased noise in the reconstructed PET images, which impacts the image quality to a certain extent. In this paper, in order to reduce the radiation exposure while maintaining the high quality of PET images, we propose a novel method based on 3D conditional generative adversarial networks (3D c-GANs) to estimate the high-quality full-dose PET images from low-dose ones. Generative adversarial networks (GANs) include a generator network and a discriminator network which are trained simultaneously with the goal of one beating the other. Similar to GANs, in the proposed 3D c-GANs, we condition the model on an input low-dose PET image and generate a corresponding output full-dose PET image. Specifically, to render the same underlying information between the low-dose and full-dose PET images, a 3D U-net-like deep architecture which can combine hierarchical features by using skip connection is designed as the generator network to synthesize the full-dose image. In order to guarantee the synthesized PET image to be close to the real one, we take into account of the estimation error loss in addition to the discriminator feedback to train the generator network. Furthermore, a concatenated 3D c-GANs based progressive refinement scheme is also proposed to further improve the quality of estimated images. Validation was done on a real human brain dataset including both the normal subjects and the subjects diagnosed as mild cognitive impairment (MCI). Experimental results show that our proposed 3D c-GANs method outperforms the benchmark methods and achieves much better performance than the state-of-the-art methods in both qualitative and quantitative measures.}, journal={NEUROIMAGE}, author={Wang, Yan and Yu, Biting and Wang, Lei and Zu, Chen and Lalush, David S. and Lin, Weili and Wu, Xi and Zhou, Jiliu and Shen, Dinggang and Zhou, Luping}, year={2018}, month={Jul}, pages={550–562} }
 @article{wang_zhou_wang_yu_zu_lalush_lin_wu_zhou_shen_2018, title={Locality Adaptive Multi-modality GANs for High-Quality PET Image Synthesis}, volume={11070}, ISBN={["978-3-030-00927-4"]}, ISSN={["1611-3349"]}, DOI={10.1007/978-3-030-00928-1_38}, abstractNote={Positron emission topography (PET) has been substantially used in recent years. To minimize the potential health risks caused by the tracer radiation inherent to PET scans, it is of great interest to synthesize the high-quality full-dose PET image from the low-dose one to reduce the radiation exposure while maintaining the image quality. In this paper, we propose a locality adaptive multi-modality generative adversarial networks model (LA-GANs) to synthesize the full-dose PET image from both the low-dose one and the accompanying T1-weighted MRI to incorporate anatomical information for better PET image synthesis. This paper has the following contributions. First, we propose a new mechanism to fuse multi-modality information in deep neural networks. Different from the traditional methods that treat each image modality as an input channel and apply the same kernel to convolute the whole image, we argue that the contributions of different modalities could vary at different image locations, and therefore a unified kernel for a whole image is not appropriate. To address this issue, we propose a method that is locality adaptive for multimodality fusion. Second, to learn this locality adaptive fusion, we utilize 1 × 1 × 1 kernel so that the number of additional parameters incurred by our method is kept minimum. This also naturally produces a fused image which acts as a pseudo input for the subsequent learning stages. Third, the proposed locality adaptive fusion mechanism is learned jointly with the PET image synthesis in an end-to-end trained 3D conditional GANs model developed by us. Our 3D GANs model generates high quality PET images by employing large-sized image patches and hierarchical features. Experimental results show that our method outperforms the traditional multi-modality fusion methods used in deep networks, as well as the state-of-the-art PET estimation approaches.}, journal={MEDICAL IMAGE COMPUTING AND COMPUTER ASSISTED INTERVENTION - MICCAI 2018, PT I}, author={Wang, Yan and Zhou, Luping and Wang, Lei and Yu, Biting and Zu, Chen and Lalush, David S. and Lin, Weili and Wu, Xi and Zhou, Jiliu and Shen, Dinggang}, year={2018}, pages={329–337} }
 @article{pietrosimone_pfeiffer_harkey_wallace_hunt_blackburn_lalush_nissman_spang_2018, title={Quadriceps weakness is associated with lesser proteoglycan density in the medial femoral cartilage six-months following anterior cruciate ligament reconstruction}, volume={26}, ISSN={1063-4584}, url={http://dx.doi.org/10.1016/J.JOCA.2018.02.733}, DOI={10.1016/J.JOCA.2018.02.733}, abstractNote={Purpose: Quadriceps weakness is a common clinical impairment that persists following anterior cruciate ligament reconstruction (ACLR). Patients with weaker quadriceps report greater disability and demonstrate aberrant knee biomechanics during walking gait, which may contribute to the development of posttraumatic knee osteoarthritis (PTOA). Specifically, the diminished capacity to eccentrically contract the quadriceps may result in increased compressive forces and suboptimal energy attenuation about the tibiofemoral joint. Weaker quadriceps is associated with greater radiographic tibiofemoral joint space narrowing four years following ACLR. Unfortunately, little is known regarding how quadriceps weakness associates with early deleterious tissue changes, including diminished proteoglycan density of the femoral cartilage, following ACLR. The purpose of our study was to determine if isometric quadriceps strength was associated with proteoglycan density of the articular cartilage, measured with T1ρ magnetic resonance imaging (MRI) relaxation times, in the medial and lateral femoral condyles of the ACLR and contralateral uninjured limbs 6 months following ACLR. Methods: NTwenty-seven individuals with a unilateral ACLR participated in the study (12 males, 15 females; 21.7 ± 3.5 years old; 175.4 ± 11.24 cm tall; 73.31 ± 13.3 kg of mass). Bilateral isometric quadriceps strength was assessed using a HUMAC Norm dynamometer at 90° of knee flexion and normalized to body mass (Nm/kg). Bilateral MRI were assessed with either a Siemens Magnetom TIM Trio 3 Tesla scanner with a 4-channel Siemens large flex coil (n = 17) or a Siemens Magnetom Prisma 3T PowerPack scanner with a XR 80/200 gradient coil (n = 10, 60 cm × 213 cm). Strong inter-scanner reliability was found for T1ρ relaxation times in the medial (ICC 2,1 = 0.99) and lateral (ICC 2,1 = 0.96) femoral condyles. Greater mean T1ρ relaxation times correspond with lesser proteoglycan density. Medial and lateral weight bearing regions of the femoral condyles (MFC and LFC) were defined as the articular cartilage between the posterior edge of the posterior horn of the meniscus and the anterior edge of the anterior horn of the meniscus in the sagittal plane. We further sub-sectioned the weight bearing portions of the articular cartilage into three regions of interest (ROI): 1) the cartilage that corresponds with the posterior horn of the meniscus (Posterior); 2) the cartilage between the anterior and posterior meniscus (Central); and 3) the cartilage corresponding with the anterior horn of the meniscus (Anterior). Separate, univariate linear regression models were used to determine the association between quadriceps strength in each limb and T1ρ relaxation times in the entire weight bearing MFC and LFC, as well as the posterior, central, and anterior ROI (P < 0.05). Results: In the ACLR limb, weaker quadriceps were associated with greater T1ρ relaxation times of the entire weight-bearing MFC (R2 = 0.14, P = 0.05) and the Anterior-MFC ROI (R2 = 0.22, P = 0.02). No significant associations were found between T1ρ relaxation times for the Central-MFC, Posterior-MFC, or any LFC articular cartilage ROIs and quadriceps strength in the ACLR limb. There were no statistically significant associations between MFC and LFC T1ρ relaxation times and quadriceps strength in the uninjured limb. We conducted a post hoc analysis of a subgroup (n = 18) without concomitant MFC articular cartilage or meniscus injury; in this subgroup, lesser strength was associated with greater T1ρ relaxation times in the entire weight bearing portion of the MFC for both the ACLR (R2 = 0.44, P = 0.04) and uninjured limbs (R2 = 0.24, P = 0.04). In these 18 participants, greater T1ρ relaxation times in the Anterior (R2 = 0.33, P = 0.03) and Central-MFC (R2 = 0.22, P = 0.05) were associated with weaker quadriceps of the ACLR limb. For the subgroup with concomitant MFC articular cartilage or meniscus injury (n = 9), there were no statistically significant associations between strength and T1ρ relaxation times in any of the MFC and LFC ROIs for the ACLR or uninjured limbs. Conclusions: Overall, our study demonstrated that lesser quadriceps strength is associated with lesser proteoglycan density in the articular cartilage of the MFC only 6 months following ACLR. The relationship between strength and MFC proteoglycan density may be strongest in individuals without concomitant articular cartilage or meniscal injury. Therefore, maximizing quadriceps strength early following ACLR may be important for minimizing early deleterious changes in articular cartilage composition, which may be related to the development of future PTOA.}, journal={Osteoarthritis and Cartilage}, publisher={Elsevier BV}, author={Pietrosimone, B. and Pfeiffer, S. and Harkey, M. and Wallace, K. and Hunt, C. and Blackburn, T. and Lalush, D. and Nissman, D. and Spang, J.}, year={2018}, month={Apr}, pages={S372–S373} }
 @article{lalush_2017, title={Magnetic Resonance-Derived Improvements on PET Imaging}, volume={25}, ISSN={["1557-9786"]}, DOI={10.1016/j.mric.2016.12.002}, abstractNote={Simultaneous PET-MR imaging improves deficiencies in PET images. The primary areas in which magnetic resonance (MR) has been applied to guide PET results are in correction for patient motion and in improving the effects of PET resolution and partial volume averaging. MR-guided motion correction of PET has been applied to respiratory, cardiac, and gross body movements and shown to improve lesion detectability and contrast. Partial volume correction or resolution improvement of PET governed by MR imaging anatomic information improves visualization of structures and quantitative accuracy. Evaluation in clinical applications is needed to determine their true impacts.}, number={2}, journal={MAGNETIC RESONANCE IMAGING CLINICS OF NORTH AMERICA}, author={Lalush, David S.}, year={2017}, month={May}, pages={257-+} }
 @article{wang_ma_an_shi_zhang_lalush_wu_pu_zhou_shen_2017, title={Semisupervised Tripled Dictionary Learning for Standard-Dose PET Image Prediction Using Low-Dose PET and Multimodal MRI}, volume={64}, ISSN={["1558-2531"]}, DOI={10.1109/tbme.2016.2564440}, abstractNote={Objective: To obtain high-quality positron emission tomography (PET) image with low-dose tracer injection, this study attempts to predict the standard-dose PET (S-PET) image from both its low-dose PET (L-PET) counterpart and corresponding magnetic resonance imaging (MRI). Methods: It was achieved by patch-based sparse representation (SR), using the training samples with a complete set of MRI, L-PET and S-PET modalities for dictionary construction. However, the number of training samples with complete modalities is often limited. In practice, many samples generally have incomplete modalities (i.e., with one or two missing modalities) that thus cannot be used in the prediction process. In light of this, we develop a semisupervised tripled dictionary learning (SSTDL) method for S-PET image prediction, which can utilize not only the samples with complete modalities (called complete samples) but also the samples with incomplete modalities (called incomplete samples), to take advantage of the large number of available training samples and thus further improve the prediction performance. Results: Validation was done on a real human brain dataset consisting of 18 subjects, and the results show that our method is superior to the SR and other baseline methods. Conclusion: This paper proposed a new S-PET prediction method, which can significantly improve the PET image quality with low-dose injection. Significance: The proposed method is favorable in clinical application since it can decrease the potential radiation risk for patients.}, number={3}, journal={IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING}, author={Wang, Yan and Ma, Guangkai and An, Le and Shi, Feng and Zhang, Pei and Lalush, David S. and Wu, Xi and Pu, Yifei and Zhou, Jiliu and Shen, Dinggang}, year={2017}, month={Mar}, pages={569–579} }
 @article{brooks_khandani_fielding_lin_sills_lee_arreola_milowsky_wallen_woods_et al._2016, title={Alternate Metabolic Programs Define Regional Variation of Relevant Biological Features in Renal Cell Carcinoma Progression}, volume={22}, ISSN={["1557-3265"]}, DOI={10.1158/1078-0432.ccr-15-2115}, abstractNote={Purpose: Clear cell renal cell carcinoma (ccRCC) has recently been redefined as a highly heterogeneous disease. In addition to genetic heterogeneity, the tumor displays risk variability for developing metastatic disease, therefore underscoring the urgent need for tissue-based prognostic strategies applicable to the clinical setting. We have recently employed the novel PET/magnetic resonance (MR) image modality to enrich our understanding of how tumor heterogeneity can relate to gene expression and tumor biology to assist in defining individualized treatment plans. Experimental Design: ccRCC patients underwent PET/MR imaging, and these images subsequently used to identify areas of varied intensity for sampling. Samples from 8 patients were subjected to histologic, immunohistochemical, and microarray analysis. Results: Tumor subsamples displayed a range of heterogeneity for common features of hypoxia-inducible factor expression and microvessel density, as well as for features closely linked to metabolic processes, such as GLUT1 and FBP1. In addition, gene signatures linked with disease risk (ccA and ccB) also demonstrated variable heterogeneity, with most tumors displaying a dominant panel of features across the sampled regions. Intriguingly, the ccA- and ccB-classified samples corresponded with metabolic features and functional imaging levels. These correlations further linked a variety of metabolic pathways (i.e., the pentose phosphate and mTOR pathways) with the more aggressive, and glucose avid ccB subtype. Conclusions: Higher tumor dependency on exogenous glucose accompanies the development of features associated with the poor risk ccB subgroup. Linking these panels of features may provide the opportunity to create functional maps to enable enhanced visualization of the heterogeneous biologic processes of an individual's disease. Clin Cancer Res; 22(12); 2950–9. ©2016 AACR.}, number={12}, journal={CLINICAL CANCER RESEARCH}, author={Brooks, Samira A. and Khandani, Amir H. and Fielding, Julia R. and Lin, Weili and Sills, Tiffany and Lee, Yueh and Arreola, Alexandra and Milowsky, Mathew I. and Wallen, Eric M. and Woods, Michael E. and et al.}, year={2016}, month={Jun}, pages={2950–2959} }
 @article{merrill_krajewski_yuan_frank_lalush_patterson_veleva_2016, title={Data on biodistribution and radiation absorbed dose profile of a novel 64Cu-labeled high affinity cell-specific peptide for positron emission tomography imaging of tumor vasculature}, volume={7}, ISSN={2352-3409}, url={http://dx.doi.org/10.1016/J.DIB.2016.02.080}, DOI={10.1016/J.DIB.2016.02.080}, abstractNote={New peptide-based diagnostic and therapeutic approaches hold promise for highly selective targeting of cancer leading to more precise and effective diagnostic and therapeutic modalities. An important feature of these approaches is to reach the tumor tissue while limiting or minimizing the dose to normal organs. In this context, efforts to design and engineer materials with optimal in vivo targeting and clearance properties are important. This Data In Brief article reports on biodistribution and radiation absorbed dose profile of a novel high affinity radiopeptide specific for bone marrow-derived tumor vasculature. Background information on the design, preparation, and in vivo characterization of this peptide-based targeted radiodiagnostic is described in the article "Synthesis and comparative evaluation of novel 64Cu-labeled high affinity cell-specific peptides for positron emission tomography of tumor vasculature" (Merrill et al., 2016) [1]. Here we report biodistribution measurements in mice and calculate the radiation absorbed doses to normal organs using a modified Medical Internal Radiation Dosimetry (MIRD) methodology that accounts for physical and geometric factors and cross-organ beta doses.}, journal={Data in Brief}, publisher={Elsevier BV}, author={Merrill, Joseph R. and Krajewski, Krzysztof and Yuan, Hong and Frank, Jonathan E. and Lalush, David S. and Patterson, Cam and Veleva, Anka N.}, year={2016}, month={Jun}, pages={480–484} }
 @article{an_zhang_adeli_wang_ma_shi_lalush_lin_shen_2016, title={Multi-Level Canonical Correlation Analysis for Standard-Dose PET Image Estimation}, volume={25}, ISSN={["1941-0042"]}, DOI={10.1109/tip.2016.2567072}, abstractNote={Positron emission tomography (PET) images are widely used in many clinical applications, such as tumor detection and brain disorder diagnosis. To obtain PET images of diagnostic quality, a sufficient amount of radioactive tracer has to be injected into a living body, which will inevitably increase the risk of radiation exposure. On the other hand, if the tracer dose is considerably reduced, the quality of the resulting images would be significantly degraded. It is of great interest to estimate a standard-dose PET (S-PET) image from a low-dose one in order to reduce the risk of radiation exposure and preserve image quality. This may be achieved through mapping both S-PET and low-dose PET data into a common space and then performing patch-based sparse representation. However, a one-size-fits-all common space built from all training patches is unlikely to be optimal for each target S-PET patch, which limits the estimation accuracy. In this paper, we propose a data-driven multi-level canonical correlation analysis scheme to solve this problem. In particular, a subset of training data that is most useful in estimating a target S-PET patch is identified in each level, and then used in the next level to update common space and improve estimation. In addition, we also use multi-modal magnetic resonance images to help improve the estimation with complementary information. Validations on phantom and real human brain data sets show that our method effectively estimates S-PET images and well preserves critical clinical quantification measures, such as standard uptake value.}, number={7}, journal={IEEE TRANSACTIONS ON IMAGE PROCESSING}, author={An, Le and Zhang, Pei and Adeli, Ehsan and Wang, Yan and Ma, Guangkai and Shi, Feng and Lalush, David S. and Lin, Weili and Shen, Dinggang}, year={2016}, month={Jul}, pages={3303–3315} }
 @article{wang_zhang_an_ma_kang_shi_wu_zhou_lalush_lin_et al._2016, title={Predicting standard-dose PET image from low-dose PET and multimodal MR images using mapping-based sparse representation}, volume={61}, ISSN={0031-9155 1361-6560}, url={http://dx.doi.org/10.1088/0031-9155/61/2/791}, DOI={10.1088/0031-9155/61/2/791}, abstractNote={Positron emission tomography (PET) has been widely used in clinical diagnosis for diseases and disorders. To obtain high-quality PET images requires a standard-dose radionuclide (tracer) injection into the human body, which inevitably increases risk of radiation exposure. One possible solution to this problem is to predict the standard-dose PET image from its low-dose counterpart and its corresponding multimodal magnetic resonance (MR) images. Inspired by the success of patch-based sparse representation (SR) in super-resolution image reconstruction, we propose a mapping-based SR (m-SR) framework for standard-dose PET image prediction. Compared with the conventional patch-based SR, our method uses a mapping strategy to ensure that the sparse coefficients, estimated from the multimodal MR images and low-dose PET image, can be applied directly to the prediction of standard-dose PET image. As the mapping between multimodal MR images (or low-dose PET image) and standard-dose PET images can be particularly complex, one step of mapping is often insufficient. To this end, an incremental refinement framework is therefore proposed. Specifically, the predicted standard-dose PET image is further mapped to the target standard-dose PET image, and then the SR is performed again to predict a new standard-dose PET image. This procedure can be repeated for prediction refinement of the iterations. Also, a patch selection based dictionary construction method is further used to speed up the prediction process. The proposed method is validated on a human brain dataset. The experimental results show that our method can outperform benchmark methods in both qualitative and quantitative measures.}, number={2}, journal={Physics in Medicine and Biology}, publisher={IOP Publishing}, author={Wang, Yan and Zhang, Pei and An, Le and Ma, Guangkai and Kang, Jiayin and Shi, Feng and Wu, Xi and Zhou, Jiliu and Lalush, David S and Lin, Weili and et al.}, year={2016}, month={Jan}, pages={791–812} }
 @article{merrill_krajewski_yuan_frank_lalush_patterson_veleva_2016, title={Synthesis and comparative evaluation of novel Cu-64-labeled high affinity cell-specific peptides for positron emission tomography imaging of tumor vasculature}, volume={84}, ISSN={["1878-5905"]}, DOI={10.1016/j.biomaterials.2016.01.031}, abstractNote={Tumor angiogenesis, the formation of new tumor blood supply, has been recognized as a hallmark of cancer and represents an important target for clinical management of various angiogenesis-dependent solid tumors. Previously, by screening a bacteriophage peptide library we have discovered the FHT-peptide sequence that binds specifically to bone marrow-derived tumor vasculature with high affinity. Here in an effort to determine the potential of the FHT-peptide for in vivo positron emission tomography (PET) imaging of aggressive tumor vasculature we studied four FHT-derivatives: NOTA-FHT, NOTA-(FHT)2, NOTA-PEG-FHT, and NOTA-PEG-(FHT)2. These peptide analogs were synthesized, labeled with the PET radionuclide (64)Cu, and characterized side-by-side with small animal PET and computed tomography imaging (microPET/CT) at 1 h, 4 h, and 24 h post injection in a subcutaneous Lewis lung carcinoma (LLC) tumor model. Because of its excellent in vivo kinetic properties and high tumor-to-background ratio, the (64)Cu-NOTA-FHT radiopeptide was selected for more detailed evaluation. Blocking studies with excess of unlabeled peptide showed specific and peptide mediated (64)Cu-NOTA-FHT tumor uptake. Biodistribution experiments in the same tumor model confirmed microPET/CT imaging results. Human radiation absorbed dose extrapolated from rodent biodistribution of (64)Cu-NOTA-FHT revealed favorable dosimetry profile. The findings from this investigation warrant further development of (64)Cu-NOTA-FHT as a potential targeted diagnostic radiopharmaceutical for PET imaging of aggressive tumor vasculature.}, journal={BIOMATERIALS}, author={Merrill, Joseph R. and Krajewski, Krzysztof and Yuan, Hong and Frank, Jonathan E. and Lalush, David S. and Patterson, Cam and Veleva, Anka N.}, year={2016}, month={Apr}, pages={241–249} }
 @inbook{an_zhang_adeli-mosabbeb_wang_ma_shi_lalush_lin_shen_2015, title={A Multi-level Canonical Correlation Analysis Scheme for Standard-Dose PET Image Estimation}, ISBN={9783319281933 9783319281940}, ISSN={0302-9743 1611-3349}, url={http://dx.doi.org/10.1007/978-3-319-28194-0_1}, DOI={10.1007/978-3-319-28194-0_1}, abstractNote={In order to obtain positron emission tomography (PET) image with diagnostic quality, we seek to estimate a standard-dose PET (S-PET) image from its low-dose counterpart (L-PET), instead of obtaining the S-PET image directly by injecting standard-dose radioactive tracer to the patient. Therefore, the risk of radiation exposure can be significantly reduced. To achieve this goal, one possible way is to first map both S-PET and L-PET data into a common space and then perform a patch-based estimation of S-PET from L-PET patches. However, the approach of using all training data to globally learn the common space may not lead to an optimal estimation of a particular target S-PET patch. In this paper, we introduce a data-driven multi-level Canonical Correlation Analysis (m-CCA) scheme to tackle this problem. Specifically, a subset of training data that are most useful in estimating a target S-PET patch are identified in each level, and using these selected training data in the subsequent level leads to more accurate common space mapping and improved estimation. In addition, we also leverage multi-modal magnetic resonance (MR) images to provide complementary information to the estimation from L-PET. Validation on a real human brain dataset demonstrates the advantage of our method as compared to other techniques.}, booktitle={Patch-Based Techniques in Medical Imaging}, publisher={Springer International Publishing}, author={An, Le and Zhang, Pei and Adeli-Mosabbeb, Ehsan and Wang, Yan and Ma, Guangkai and Shi, Feng and Lalush, David S. and Lin, Weili and Shen, Dinggang}, year={2015}, pages={1–9} }
 @article{juttukonda_mersereau_chen_su_rubin_benzinger_lalush_an_2015, title={MR-based attenuation correction for PET/MRI neurological studies with continuous-valued attenuation coefficients for bone through a conversion from R2*to CT-Hounsfield units}, volume={112}, ISSN={["1095-9572"]}, DOI={10.1016/j.neuroimage.2015.03.009}, abstractNote={MR-based correction for photon attenuation in PET/MRI remains challenging, particularly for neurological applications requiring quantitation of data. Existing methods are either not sufficiently accurate or are limited by the computation time required. The goal of this study was to develop an MR-based attenuation correction method that accurately separates bone tissue from air and provides continuous-valued attenuation coefficients for bone.PET/MRI and CT datasets were obtained from 98 subjects (mean age [±SD]: 66yrs [±9.8], 57 females) using an IRB-approved protocol and with informed consent. Subjects were injected with 352±29MBq of (18)F-Florbetapir tracer, and PET acquisitions were begun either immediately or 50min after injection. CT images of the head were acquired separately using a PET/CT system. Dual echo ultrashort echo-time (UTE) images and two-point Dixon images were acquired. Regions of air were segmented via a threshold of the voxel-wise multiplicative inverse of the UTE echo 1 image. Regions of bone were segmented via a threshold of the R2* image computed from the UTE echo 1 and UTE echo 2 images. Regions of fat and soft tissue were segmented using fat and water images decomposed from the Dixon images. Air, fat, and soft tissue were assigned linear attenuation coefficients (LACs) of 0, 0.092, and 0.1cm(-1), respectively. LACs for bone were derived from a regression analysis between corresponding R2* and CT values. PET images were reconstructed using the gold standard CT method and the proposed CAR-RiDR method.The RiDR segmentation method produces mean Dice coefficient±SD across subjects of 0.75±0.05 for bone and 0.60±0.08 for air. The CAR model for bone LACs greatly improves accuracy in estimating CT values (28.2%±3.0 mean error) compared to the use of a constant CT value (46.9%±5.8, p<10(-6)). Finally, the CAR-RiDR method provides a low whole-brain mean absolute percent-error (MAPE±SD) in PET reconstructions across subjects of 2.55%±0.86. Regional PET errors were also low and ranged from 0.88% to 3.79% in 24 brain ROIs.We propose an MR-based attenuation correction method (CAR-RiDR) for quantitative PET neurological imaging. The proposed method employs UTE and Dixon images and consists of two novel components: 1) accurate segmentation of air and bone using the inverse of the UTE1 image and the R2* image, respectively and 2) estimation of continuous LAC values for bone using a regression between R2* and CT-Hounsfield units. From our analysis, we conclude that the proposed method closely approaches (<3% error) the gold standard CT-scaled method in PET reconstruction accuracy.}, journal={NEUROIMAGE}, author={Juttukonda, Meher R. and Mersereau, Bryant G. and Chen, Yasheng and Su, Yi and Rubin, Brian G. and Benzinger, Tammie L. S. and Lalush, David S. and An, Hongyu}, year={2015}, month={May}, pages={160–168} }
 @inbook{wang_zhang_an_ma_kang_wu_zhou_lalush_lin_shen_2015, title={Predicting Standard-Dose PET Image from Low-Dose PET and Multimodal MR Images Using Mapping-Based Sparse Representation}, ISBN={9783319248875 9783319248882}, ISSN={0302-9743 1611-3349}, url={http://dx.doi.org/10.1007/978-3-319-24888-2_16}, DOI={10.1007/978-3-319-24888-2_16}, abstractNote={Positron emission tomography (PET) has been widely used in clinical diagnosis of diseases or disorders. To reduce the risk of radiation exposure, we propose a mapping-based sparse representation (m-SR) framework for prediction of standard-dose PET image from its low-dose counterpart and corresponding multimodal magnetic resonance (MR) images. Compared with the conventional patch-based SR, our method uses a mapping strategy to ensure that the sparse coefficients estimated from the low-dose PET and multimodal MR images could be directly applied to the prediction of standard-dose PET images. An incremental refinement framework is also proposed to further improve the performance. Finally, a patch selection based dictionary construction method is used to speed up the prediction process. The proposed method has been validated on a real human brain dataset, showing that our method can work much better than the state-of-the-art method both qualitatively and quantitatively.}, booktitle={Machine Learning in Medical Imaging}, publisher={Springer International Publishing}, author={Wang, Yan and Zhang, Pei and An, Le and Ma, Guangkai and Kang, Jiayin and Wu, Xi and Zhou, Jiliu and Lalush, David S. and Lin, Weili and Shen, Dinggang}, year={2015}, pages={127–135} }
 @article{kang_gao_shi_lalush_lin_shen_2015, title={Prediction of standard-dose brain PET image by using MRI and low-dose brain [F-18]FDG PET images}, volume={42}, ISSN={["2473-4209"]}, DOI={10.1118/1.4928400}, abstractNote={PURPOSE
Positron emission tomography (PET) is a nuclear medical imaging technology that produces 3D images reflecting tissue metabolic activity in human body. PET has been widely used in various clinical applications, such as in diagnosis of brain disorders. High-quality PET images play an essential role in diagnosing brain diseases/disorders. In practice, in order to obtain high-quality PET images, a standard-dose radionuclide (tracer) needs to be used and injected into a living body. As a result, it will inevitably increase the patient's exposure to radiation. One solution to solve this problem is predicting standard-dose PET images using low-dose PET images. As yet, no previous studies with this approach have been reported. Accordingly, in this paper, the authors propose a regression forest based framework for predicting a standard-dose brain [(18)F]FDG PET image by using a low-dose brain [(18)F]FDG PET image and its corresponding magnetic resonance imaging (MRI) image.


METHODS
The authors employ a regression forest for predicting the standard-dose brain [(18)F]FDG PET image by low-dose brain [(18)F]FDG PET and MRI images. Specifically, the proposed method consists of two main steps. First, based on the segmented brain tissues (i.e., cerebrospinal fluid, gray matter, and white matter) in the MRI image, the authors extract features for each patch in the brain image from both low-dose PET and MRI images to build tissue-specific models that can be used to initially predict standard-dose brain [(18)F]FDG PET images. Second, an iterative refinement strategy, via estimating the predicted image difference, is used to further improve the prediction accuracy.


RESULTS
The authors evaluated their algorithm on a brain dataset, consisting of 11 subjects with MRI, low-dose PET, and standard-dose PET images, using leave-one-out cross-validations. The proposed algorithm gives promising results with well-estimated standard-dose brain [(18)F]FDG PET image and substantially enhanced image quality of low-dose brain [(18)F]FDG PET image.


CONCLUSIONS
In this paper, the authors propose a framework to generate standard-dose brain [(18)F]FDG PET image using low-dose brain [(18)F]FDG PET and MRI images. Both the visual and quantitative results indicate that the standard-dose brain [(18)F]FDG PET can be well-predicted using MRI and low-dose brain [(18)F]FDG PET.}, number={9}, journal={MEDICAL PHYSICS}, author={Kang, Jiayin and Gao, Yaozong and Shi, Feng and Lalush, David S. and Lin, Weili and Shen, Dinggang}, year={2015}, month={Sep}, pages={5301–5309} }
 @article{rodríguez_liao_he_schisler_newgard_drujan_glass_frederick_yoder_lalush_et al._2015, title={The ubiquitin ligase MuRF1 regulates PPARα activity in the heart by enhancing nuclear export via monoubiquitination}, volume={413}, ISSN={0303-7207}, url={http://dx.doi.org/10.1016/J.MCE.2015.06.008}, DOI={10.1016/J.MCE.2015.06.008}, abstractNote={The transcriptional regulation of peroxisome proliferator-activated receptor (PPAR) α by post-translational modification, such as ubiquitin, has not been described. We report here for the first time an ubiquitin ligase (muscle ring finger-1/MuRF1) that inhibits fatty acid oxidation by inhibiting PPARα, but not PPARβ/δ or PPARγ in cardiomyocytes in vitro. Similarly, MuRF1 Tg+ hearts showed significant decreases in nuclear PPARα activity and acyl-carnitine intermediates, while MuRF1-/- hearts exhibited increased PPARα activity and acyl-carnitine intermediates. MuRF1 directly interacts with PPARα, mono-ubiquitinates it, and targets it for nuclear export to inhibit fatty acid oxidation in a proteasome independent manner. We then identified a previously undescribed nuclear export sequence in PPARα, along with three specific lysines (292, 310, 388) required for MuRF1's targeting of nuclear export. These studies identify the role of ubiquitination in regulating cardiac PPARα, including the ubiquitin ligase that may be responsible for this critical regulation of cardiac metabolism in heart failure.}, journal={Molecular and Cellular Endocrinology}, publisher={Elsevier BV}, author={Rodríguez, Jessica E. and Liao, Jie-Ying and He, Jun and Schisler, Jonathan C. and Newgard, Christopher B. and Drujan, Doreen and Glass, David J. and Frederick, C. Brandon and Yoder, Bryan C. and Lalush, David S. and et al.}, year={2015}, month={Sep}, pages={36–48} }
 @article{charoenpanich_wall_tucker_andrews_lalush_dirschl_loboa_2014, title={Cyclic Tensile Strain Enhances Osteogenesis and Angiogenesis in Mesenchymal Stem Cells from Osteoporotic Donors}, volume={20}, ISSN={["1937-335X"]}, DOI={10.1089/ten.tea.2013.0006}, abstractNote={We have shown that the uniaxial cyclic tensile strain of magnitude 10% promotes and enhances osteogenesis of human mesenchymal stem cells (hMSC) and human adipose-derived stem cells (hASC) from normal, nonosteoporotic donors. In the present study, MSC from osteoporotic donors were analyzed for changes in mRNA expression in response to 10% uniaxial tensile strain to identify potential mechanisms underlying the use of this mechanical loading paradigm for prevention and treatment of osteoporosis. Human MSC isolated from three female, postmenopausal osteoporotic donors were analyzed for their responses to mechanical loading using microarray analysis of over 47,000 gene probes. Human MSC were seeded in three-dimensional collagen type I constructs to mimic the organic extracellular matrix of bone and 10% uniaxial cyclic tensile strain was applied to promote osteogenesis. Seventy-nine genes were shown to be regulated within hMSC from osteoporotic donors in response to 10% cyclic tensile strain. Upregulation of six genes were further confirmed with real-time RT-PCR: jun D proto-oncogene (JUND) and plasminogen activator, urokinase receptor (PLAUR), two genes identified as potential key molecules from network analysis; phosphoinositide-3-kinase, catalytic, delta polypeptide (PIK3CD) and wingless-type MMTV integration site family, member 5B (WNT5B), two genes with known importance in bone biology; and, PDZ and LIM domain 4 (PDLIM4) and vascular endothelial growth factor A (VEGFA), two genes that we have previously shown are significantly regulated in hASC in response to this mechanical stimulus. Function analysis indicated that 10% cyclic tensile strain induced expression of genes associated with cell movement, cell proliferation, and tissue development, including development in musculoskeletal and cardiovascular systems. Our results demonstrate that hMSC from aged, osteoporotic donors are capable of enhanced osteogenic differentiation in response to 10% cyclic tensile strain with significant increases in the expression of genes associated with enhanced cell proliferation, musculoskeletal development, and angiogenesis. Surprisingly, cyclic tensile strain of magnitude 10% not only enhanced osteogenesis in hMSC from osteoporotic donors, but also enhanced expression of angiogenic factors. Better understanding and methodologies to promote osteogenesis in hMSC from elderly, osteoporotic donors may greatly facilitate achieving long-term success in bone regeneration and functional bone tissue engineering for this ever-growing patient population.}, number={1-2}, journal={TISSUE ENGINEERING PART A}, author={Charoenpanich, Adisri and Wall, Michelle E. and Tucker, Charles J. and Andrews, Danica M. K. and Lalush, David S. and Dirschl, Douglas R. and Loboa, Elizabeth G.}, year={2014}, month={Jan}, pages={67–78} }
 @article{patterson_frederick_yuan_dyer_lockyer_lalush_veleva_2013, title={Development of a New Positron Emission Tomography Tracer for Targeting Tumor Angiogenesis: Synthesis, Small Animal Imaging, and Radiation Dosimetry}, volume={18}, ISSN={["1420-3049"]}, DOI={10.3390/molecules18055594}, abstractNote={Angiogenesis plays a key role in cancer progression and correlates with disease aggressiveness and poor clinical outcomes. Affinity ligands discovered by screening phage display random peptide libraries can be engineered to molecularly target tumor blood vessels for noninvasive imaging and early detection of tumor aggressiveness. In this study, we tested the ability of a phage-display-selected peptide sequence recognizing specifically bone marrow- derived pro-angiogenic tumor-homing cells, the QFP-peptide, radiolabeled with 64Cu radioisotope to selectively image tumor vasculature in vivo by positron emission tomography (PET). To prepare the targeted PET tracer we modified QFP-phage with the DOTA chelator and radiolabeled the purified QFP-phage-DOTA intermediate with 64Cu to obtain QFP-targeted radioconjugate with high radiopharmaceutical yield and specific activity. We evaluated the new PET tracer in vivo in a subcutaneous (s.c.) Lewis lung carcinoma (LLC) mouse model and conducted tissue distribution, small animal PET/CT imaging study, autoradiography, histology, fluorescence imaging, and dosimetry assessments. The results from this study show that, in the context of the s.c. LLC immunocompetent mouse model, the QFP-tracer can target tumor blood vessels selectively. However, further optimization of the biodistribution and dosimetry profile of the tracer is necessary to ensure efficient radiopharmaceutical applications enabled by the biological specificity of the QFP-peptide.}, number={5}, journal={MOLECULES}, author={Patterson, Cam and Frederick, C. Brandon and Yuan, Hong and Dyer, Laura A. and Lockyer, Pamela and Lalush, David S. and Veleva, Anka N.}, year={2013}, month={May}, pages={5594–5610} }
 @article{gonzales_lalush_2012, title={Eigenvector decomposition of full-spectrum x-ray computed tomography}, volume={57}, ISSN={["1361-6560"]}, DOI={10.1088/0031-9155/57/5/1309}, abstractNote={Energy-discriminated x-ray computed tomography (CT) data were projected onto a set of basis functions to suppress the noise in filtered back-projection (FBP) reconstructions. The x-ray CT data were acquired using a novel x-ray system which incorporated a single-pixel photon-counting x-ray detector to measure the x-ray spectrum for each projection ray. A matrix of the spectral response of different materials was decomposed using eigenvalue decomposition to form the basis functions. Projection of FBP onto basis functions created a de facto image segmentation of multiple contrast agents. Final reconstructions showed significant noise suppression while preserving important energy-axis data. The noise suppression was demonstrated by a marked improvement in the signal-to-noise ratio (SNR) along the energy axis for multiple regions of interest in the reconstructed images. Basis functions used on a more coarsely sampled energy axis still showed an improved SNR. We conclude that the noise–resolution trade off along the energy axis was significantly improved using the eigenvalue decomposition basis functions.}, number={5}, journal={PHYSICS IN MEDICINE AND BIOLOGY}, author={Gonzales, Brian J. and Lalush, David S.}, year={2012}, month={Mar}, pages={1309–1323} }
 @article{veleva_nepal_frederick_schwab_lockyer_yuan_lalush_patterson_2011, title={Efficient In Vivo Selection of a Novel Tumor-Associated Peptide from a Phage Display Library}, volume={16}, ISSN={["1420-3049"]}, DOI={10.3390/molecules160109}, abstractNote={We developed a screening procedure to identify ligands from a phage display random peptide library that are selective for circulating bone marrow derived cells homing to angiogenic tumors. Panning the library on blood outgrowth endothelial cell suspension in vitro followed by in vivo selection based on homing of bone marrow-bound phage to angiogenic tumors, yielded the peptide QFPPKLTNNSML. Upon intravenous injection phage displaying this peptide homed to Lewis lung carcinoma (LLC) tumors in vivo whereas control phage did not localize to tumor tissue. Phage carrying the QFPPKLTNNSML peptide labeled with 64Cu radionuclide when administered intravenously into a tumor bearing mouse was detected noninvasively with positron emission tomography (PET) around the tumor. These proof-of-principle experiments demonstrate the ability of the QFPPKLTNNSML peptide to deliver payload (radiolabeled phage conjugates) in vivo to sites of ongoing angiogenesis and point to its potential clinical utility in a variety of physiologic and pathologic processes where neovascular growth is a critical component.}, number={1}, journal={MOLECULES}, author={Veleva, Anka N. and Nepal, Desh B. and Frederick, C. Brandon and Schwab, Jacob and Lockyer, Pamela and Yuan, Hong and Lalush, David S. and Patterson, Cam}, year={2011}, month={Jan}, pages={900–914} }
 @article{gonzales_lalush_2011, title={Full-Spectrum CT Reconstruction Using a Weighted Least Squares Algorithm With an Energy-Axis Penalty}, volume={30}, ISSN={["1558-254X"]}, DOI={10.1109/tmi.2010.2048120}, abstractNote={Recent developments in X-ray detectors have created the potential to perform energy-sensitive X-ray computed tomography (CT); that is, to reconstruct a series of CT images associated with different X-ray energies from a single scan. In this paper we propose a penalized weighted least squares (PWLS) algorithm for reconstruction of polychromatic energy-differentiated X-ray CT data and a unique experimental setup to take energy-differentiated X-ray CT data. The experimental setup is designed to acquire a complete X-ray spectrum for every projection ray. We use these data to estimate the linear attenuation coefficient as a function of energy for every pixel in the reconstructed attenuation map. We use prior knowledge of the properties of attenuation spectra to smooth the reconstructions, significantly reducing the noise and improving the contrast-to-noise ratio (CNR) in the reconstructed images without significantly biasing the data. We conclude that this algorithm is an effective method for reconstructing energy-sensitive CT data and provides justification for further research in energy sensitive CT systems.}, number={2}, journal={IEEE TRANSACTIONS ON MEDICAL IMAGING}, author={Gonzales, Brian and Lalush, David}, year={2011}, month={Feb}, pages={173–183} }
 @article{charoenpanich_wall_tucker_andrews_lalush_loboa_2011, title={Microarray Analysis of Human Adipose-Derived Stem Cells in Three-Dimensional Collagen Culture: Osteogenesis Inhibits Bone Morphogenic Protein and Wnt Signaling Pathways, and Cyclic Tensile Strain Causes Upregulation of Proinflammatory Cytokine Regulators and Angiogenic Factors}, volume={17}, ISSN={["1937-335X"]}, DOI={10.1089/ten.tea.2011.0107}, abstractNote={Human adipose-derived stem cells (hASC) have shown great potential for bone tissue engineering. However, the molecular mechanisms underlying this potential are not yet known, in particular the separate and combined effects of three-dimensional (3D) culture and mechanical loading on hASC osteogenesis. Mechanical stimuli play a pivotal role in bone formation, remodeling, and fracture repair. To further understand hASC osteogenic differentiation and response to mechanical stimuli, gene expression profiles of proliferating or osteogenically induced hASC in 3D collagen I culture in the presence and absence of 10% uniaxial cyclic tensile strain were examined using microarray analysis. About 847 genes and 95 canonical pathways were affected during osteogenesis of hASC in 3D culture. Pathway analysis indicated the potential roles of Wnt/β-catenin signaling, bone morphogenic protein (BMP) signaling, platelet-derived growth factor (PDGF) signaling, and insulin-like growth factor 1 (IGF-1) signaling in hASC during osteogenic differentiation. Application of 10% uniaxial cyclic tensile strain suggested synergistic effects of strain with osteogenic differentiation media on hASC osteogenesis as indicated by significantly increased calcium accretion of hASC. There was no significant further alteration in the four major pathways (Wnt/β-catenin, BMP, PDGF, and IGF-1). However, 184 transcripts were affected by 10% cyclic tensile strain. Function and network analysis of these transcripts suggested that 10% cyclic tensile strain may play a role during hASC osteogenic differentiation by upregulating two crucial factors in bone regeneration: (1) proinflammatory cytokine regulators interleukin 1 receptor antagonist and suppressor of cytokine signaling 3; (2) known angiogenic inductors fibroblast growth factor 2, matrix metalloproteinase 2, and vascular endothelial growth factor A. This is the first study to investigate the effects of both 3D culture and mechanical load on hASC osteogenic differentiation. A complete microarray analysis investigating both the separate effect of soluble osteogenic inductive factors and the combined effects of chemical and mechanical stimulation was performed on hASC undergoing osteogenic differentiation. We have identified specific genes and pathways associated with mechanical response and osteogenic potential of hASC, thus providing significant information toward improved understanding of our use of hASC for functional bone tissue engineering applications.}, number={21-22}, journal={TISSUE ENGINEERING PART A}, author={Charoenpanich, Adisri and Wall, Michelle E. and Tucker, Charles J. and Andrews, Danica M. K. and Lalush, David S. and Loboa, Elizabeth G.}, year={2011}, month={Nov}, pages={2615–2627} }
 @article{quan_lalush_2010, title={Three-Dimensional Imaging Properties of Rotation-Free Square and Hexagonal Micro-CT Systems}, volume={29}, ISSN={["1558-254X"]}, DOI={10.1109/tmi.2009.2039799}, abstractNote={We study the 3-D imaging properties of a rotation-free micro-computed tomography (CT) system with square and hexagonal geometries. These systems use linear arrays of carbon-nanotube-based X-ray sources that are individually addressable. The source arrays and area detectors in the square and the hexagonal geometries form the sides of a polygon. The tomographic angular sampling for both geometries requires no motion of the sources, the detectors, or the subject. We demonstrate that the hexagonal geometry has improved angular coverage as compared to the square geometry. The ordered-subset convex iterative algorithm is implemented in both geometries for reconstructions from cone-beam projection data. Simulation studies show that both geometries can be effectively reconstructed with polychromatic or monochromatic source spectra. As a result of the incomplete tomographic sampling of the two geometries, some streaking artifacts appear in the reconstructed images. The hexagonal geometry, in general, produces fewer streaking artifacts than the square geometry. On the other hand, the two geometries perform quite similarly in resolution-noise trade-off, so we conclude that the proposed geometries are comparably effective for the rotation-free micro-CT and the hexagonal geometry is superior in reducing streaking artifacts.}, number={3}, journal={IEEE TRANSACTIONS ON MEDICAL IMAGING}, author={Quan, Enzhuo Michelle and Lalush, David S.}, year={2010}, month={Mar}, pages={916–923} }
 @article{cao_lee_peng_liu_rajaram_calderon-colon_an_wang_phan_sultana_et al._2009, title={A dynamic micro-CT scanner based on a carbon nanotube field emission x-ray source}, volume={54}, ISSN={["0031-9155"]}, DOI={10.1088/0031-9155/54/8/005}, abstractNote={Current commercial micro-CT scanners have the capability of imaging objects ex vivo with high spatial resolution, but performing in vivo micro-CT on free-breathing small animals is still challenging because their physiological motions are non-periodic and much faster than those of humans. In this paper, we present a prototype physiologically gated micro-computed tomography (micro-CT) scanner based on a carbon nanotube field emission micro-focus x-ray source. The novel x-ray source allows x-ray pulses and imaging sequences to be readily synchronized and gated to non-periodic physiological signals from small animals. The system performance is evaluated using phantoms and sacrificed and anesthetized mice. Prospective respiratory-gated micro-CT images of anesthetized free-breathing mice were collected using this scanner at 50 ms temporal resolution and 6.2 lp mm−1 at 10% system MTF. The high spatial and temporal resolutions of the micro-CT scanner make it well suited for high-resolution imaging of free-breathing small animals.}, number={8}, journal={PHYSICS IN MEDICINE AND BIOLOGY}, author={Cao, G. and Lee, Y. Z. and Peng, R. and Liu, Z. and Rajaram, R. and Calderon-Colon, X. and An, L. and Wang, P. and Phan, T. and Sultana, S. and et al.}, year={2009}, month={Apr}, pages={2323–2340} }
 @article{quan_lalush_2009, title={A faster ordered-subset convex algorithm for iterative reconstruction in a rotation-free micro-CT system}, volume={54}, ISSN={0031-9155 1361-6560}, url={http://dx.doi.org/10.1088/0031-9155/54/4/016}, DOI={10.1088/0031-9155/54/4/016}, abstractNote={We present a faster iterative reconstruction algorithm based on the ordered-subset convex (OSC) algorithm for transmission CT. The OSC algorithm was modified such that it calculates the normalization term before the iterative process in order to save computational cost. The modified version requires only one backprojection per iteration as compared to two required for the original OSC. We applied the modified OSC (MOSC) algorithm to a rotation-free micro-CT system that we proposed previously, observed its performance, and compared with the OSC algorithm for 3D cone-beam reconstruction. Measurements on the reconstructed images as well as the point spread functions show that MOSC is quite similar to OSC; in noise-resolution trade-off, MOSC is comparable with OSC in a regular-noise situation and it is slightly worse than OSC in an extremely high-noise situation. The timing record shows that MOSC saves 25–30% CPU time, depending on the number of iterations used. We conclude that the MOSC algorithm is more efficient than OSC and provides comparable images.}, number={4}, journal={Physics in Medicine and Biology}, publisher={IOP Publishing}, author={Quan, E and Lalush, D S}, year={2009}, month={Jan}, pages={1061–1072} }
 @article{connor_hallen_lalush_sumner_zhong_2009, place={UK}, title={Comparison of diffraction-enhanced computed tomography and monochromatic synchrotron radiation computed tomography of human trabecular bone}, volume={54}, ISSN={["1361-6560"]}, url={http://dx.doi.org/10.1088/0031-9155/54/20/006}, DOI={10.1088/0031-9155/54/20/006}, abstractNote={Diffraction-enhanced imaging (DEI) is an x-ray-based medical imaging modality that, when used in tomography mode (DECT), can generate a three-dimensional map of both the apparent absorption coefficient and the out-of-plane gradient of the index of refraction of the sample. DECT is known to have contrast gains over monochromatic synchrotron radiation CT (SRCT) for soft tissue structures. The goal of this experiment was to compare contrast-to-noise ratio (CNR) and resolution in images of human trabecular bone acquired using SRCT with images acquired using DECT. All images were acquired at the National Synchrotron Light Source (Upton, NY, USA) at beamline X15 A at an x-ray energy of 40 keV and the silicon [3 3 3] reflection. SRCT, apparent absorption DECT and refraction DECT slice images of the trabecular bone were created. The apparent absorption DECT images have significantly higher spatial resolution and CNR than the corresponding SRCT images. Thus, DECT will prove to be a useful tool for imaging applications in which high contrast and high spatial resolution are required for both soft tissue features and bone.}, number={20}, journal={PHYSICS IN MEDICINE AND BIOLOGY}, author={Connor, D. M. and Hallen, H. D. and Lalush, D. S. and Sumner, D. R. and Zhong, Z.}, year={2009}, month={Oct}, pages={6123–6133} }
 @article{qian_rajaram_calderon-colon_yang_phan_lalush_lu_zhou_2009, title={Design and characterization of a spatially distributed multibeam field emission x-ray source for stationary digital breast tomosynthesis}, volume={36}, ISSN={["2473-4209"]}, DOI={10.1118/1.3213520}, abstractNote={Digital breast tomosynthesis (DBT) is a limited angle computed tomography technique that can distinguish tumors from its overlying breast tissues and has potentials for detection of cancers at a smaller size and earlier stage. Current prototype DBT scanners are based on the regular full-field digital mammography systems and require partial isocentric motion of an x-ray tube over certain angular range to record the projection views. This prolongs the scanning time and, in turn, degrades the imaging quality due to motion blur. To mitigate the above limitations, the concept of a stationary DBT (s-DBT) scanner has been recently proposed based on the newly developed spatially distributed multibeam field emission x-ray (MBFEX) source technique using the carbon nanotube. The purpose of this article is to evaluate the performance of the 25-beam MBFEX source array that has been designed and fabricated for the s-DBT system. The s-DBT system records all the projection images by electronically activating the multiple x-ray beams from different viewing angles without any mechanical motion. The configuration of the MBFEX source is close to the published values from the Siemens Mammomat system. The key issues including the x-ray flux, focal spot size, spatial resolution, scanning time, beam-to-beam consistency, and reliability are evaluated using the standard procedures. In this article, the authors describe the design and performance of a distributed x-ray source array specifically designed for the s-DBT system. They evaluate the emission current, current variation, lifetime, and focal spot sizes of the source array. An emission current of up to 18 mA was obtained at 0.5 x 0.3 mm effective focal spot size. The experimentally measured focal spot sizes are comparable to that of a typical commercial mammography tube without motion blurring. Trade-off between the system spatial resolution, x-ray flux, and scanning time are also discussed. Projection images of a breast phantom were collected using the x-ray source array from 25 different viewing angles without motion. These preliminary results demonstrate the feasibility of the proposed s-DBT scanner. The technology has the potential to increase the resolution and reduce the imaging time for DBT. With the present design of 25 views, they demonstrated experimentally the feasibility of achieving 11 s scanning time at full detector resolution with 0.5 x 0.3 mm source resolution without motion blur. The flexibility in configuration of the x-ray source array will also allow system designers to consider imaging geometries that are difficult to achieve with the conventional single-source rotating approach.}, number={10}, journal={MEDICAL PHYSICS}, author={Qian, Xin and Rajaram, Ramya and Calderon-Colon, Xiomara and Yang, Guang and Phan, Tuyen and Lalush, David S. and Lu, Jianping and Zhou, Otto}, year={2009}, month={Oct}, pages={4389–4399} }
 @article{segars_lalush_frey_manocha_king_tsui_2009, title={Improved Dynamic Cardiac Phantom Based on 4D NURBS and Tagged MRI}, volume={56}, ISSN={["0018-9499"]}, DOI={10.1109/TNS.2009.2016196}, abstractNote={We previously developed a realistic phantom for the cardiac motion for use in medical imaging research. The phantom was based upon a gated magnetic resonance imaging (MRI) cardiac study and using 4D non-uniform rational b-splines (NURBS). Using the gated MRI study as the basis for the cardiac model had its limitations. From the MRI images, the change in the size and geometry of the heart structures could be obtained, but without markers to track the movement of points on or within the myocardium, no explicit time correspondence could be established for the structures. Also, only the inner and outer surfaces of the myocardium could be modeled. We enhance this phantom of the beating heart using 4D tagged MRI data. We utilize NURBS surfaces to analyze the full 3D motion of the heart from the tagged data. From this analysis, time-dependent 3D NURBS surfaces were created for the right (RV) and left ventricles (LV). Models for the atria were developed separately since the tagged data only covered the ventricles. A 4D NURBS surface was fit to the 3D surfaces of the heart creating time-continuous 4D NURBS models. Multiple 4D surfaces were created for the left ventricle (LV) spanning its entire volume. The multiple surfaces for the LV were spline-interpolated about an additional dimension, thickness, creating a 4D NURBS solid model for the LV with the ability to represent the motion of any point within the volume of the LV myocardium at any time during the cardiac cycle. Our analysis of the tagged data was found to produce accurate models for the RV and LV at each time frame. In a comparison with segmented structures from the tagged dataset, LV and RV surface predictions were found to vary by a maximum of 1.5 mm's and 3.4 mm's respectively. The errors can be attributed to the tag spacing in the data (7.97 mm's). The new cardiac model was incorporated into the 4D NURBS-based Cardiac-Torso (NCAT) phantom widely used in imaging research. With its enhanced abilities, the model will provide a useful tool in the study of cardiac imaging and the effects of cardiac motion in medical images.}, number={5}, journal={IEEE TRANSACTIONS ON NUCLEAR SCIENCE}, author={Segars, W. Paul and Lalush, David S. and Frey, Eric C. and Manocha, Dinesh and King, Michael A. and Tsui, Benjamin M. W.}, year={2009}, month={Oct}, pages={2728–2738} }
 @article{lalush_2008, title={Binary encoding of multiplexed images in mixed noise}, volume={27}, ISSN={["1558-254X"]}, DOI={10.1109/TMI.2008.922697}, abstractNote={Binary coding of multiplexed signals and images has been studied in the context of spectroscopy with models of either purely constant or purely proportional noise, and has been shown to result in improved noise performance under certain conditions. We consider the case of mixed noise in an imaging system consisting of multiple individually-controllable sources (X-ray or near-infrared, for example) shining on a single detector. We develop a mathematical model for the noise in such a system and show that the noise is dependent on the properties of the binary coding matrix and on the average number of sources used for each code. Each binary matrix has a characteristic linear relationship between the ratio of proportional-to-constant noise and the noise level in the decoded image. We introduce a criterion for noise level, which is minimized via a genetic algorithm search. The search procedure results in the discovery of matrices that outperform the Hadamard S-matrices at certain levels of mixed noise. Simulation of a seven-source radiography system demonstrates that the noise model predicts trends and rank order of performance in regions of nonuniform images and in a simple tomosynthesis reconstruction. We conclude that the model developed provides a simple framework for analysis, discovery, and optimization of binary coding patterns used in multiplexed imaging systems.}, number={9}, journal={IEEE TRANSACTIONS ON MEDICAL IMAGING}, author={Lalush, David S.}, year={2008}, month={Sep}, pages={1323–1332} }
 @article{pfeiler_lalush_loboa_2007, title={Semiautomated finite element mesh generation methods for a long bone}, volume={85}, ISSN={["1872-7565"]}, DOI={10.1016/j.cmpb.2006.10.009}, abstractNote={The objective of this work was to develop and test a semi-automated finite element mesh generation method using computed tomography (CT) image data of a canine radius. The present study employs a direct conversion from CT Hounsfield units to elastic moduli. Our method attempts to minimize user interaction and eliminate the need for mesh smoothing to produce a model suitable for finite element analysis. Validation of the computational model was conducted by loading the CT-imaged canine radius in four-point bending and using strain gages to record resultant strains that were then compared to strains calculated with the computational model. Geometry-based and uniform modulus voxel-based models were also constructed from the same imaging data set and compared. The nonuniform voxel-based model most accurately predicted the axial strain response of the sample bone (R(2)=0.9764).}, number={3}, journal={COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE}, author={Pfeiler, T. W. and Lalush, D. S. and Loboa, E. G.}, year={2007}, month={Mar}, pages={196–202} }
 @inproceedings{quan_lalush_2006, title={A faster ordered-subset convex algorithm for iterative reconstruction}, DOI={10.1109/nssmic.2006.353737}, abstractNote={We present a faster iterative reconstruction algorithm based on the ordered-subset convex (OSC) algorithm for transmission CT. The OSC algorithm was modified such that it calculates the normalization term before the iterative process in order to save computational cost. The modified version requires only one backprojection per iteration as compared to two required for the original OSC. We applied the modified OSC algorithm to a dense linear source array X-ray CT system that we proposed previously, observed its performance and compared with the original OSC and BIT algorithms. Spatial measures of point spread functions in reconstructed images show that the new algorithm is quite similar with the original algorithm; for reconstructions with simulated Poisson noise, the standard deviation of the new algorithm is slightly lower than that of the original algorithm. We conclude that the new OSC algorithm is more efficient than the original one and provides comparable images.}, booktitle={2006 ieee nuclear science symposium conference record, vol 1-6}, author={Quan, E. Z. and Lalush, D. S.}, year={2006}, pages={3424–3427} }
 @inproceedings{lalush_rajaram_quan_zhang_lu_zhou_2006, title={Three-dimensional tomosynthesis reconstruction from 1D and 2D X-ray source arrays}, DOI={10.1109/nssmic.2006.354219}, abstractNote={We study the effects of geometric design on the reconstruction of 3D images from an X-ray tomosynthesis system using microfabricated discrete X-ray sources. Carbon-nanotube-based field-emission X-ray sources can be fabricated in arrays; however, little is known about the effects of the geometry of such a system on reconstruction of tomosynthesis data. We produced simulated X-ray projection data for several source array geometries including a 1 times 11 array, and a 3 times 11 array. The phantom simulates a mammography task, with seven 400 mum spheres embedded in a uniformly-absorbing background. Data from both geometries was reconstructed using the ordered-subset convex (OSC) algorithm specially implemented for these array geometries. Reconstruction was performed on an 800 times 800 (lateral) times 20 (depth) array of noncubic voxels of size 200 mum times 200 mum (lateral) times 2.5 mm (depth). Contrast, resolution, and noise measurements on the reconstructed spheres were used to compare results from the different geometries. The reconstruction from the 2D array had higher contrast than that from the 1D array, but the 2D array image also suffered from higher levels of noise for the same total exposure. The contrast-to-noise ratio for the 2D array, was 5-17% higher than the 1D array. Other studies showed that staggering a 2D array is beneficial, and that increasing the density of sources is detrimental after a certain optimal density is reached We conclude that, in a tomosynthesis system such as that described here, a 2D source array will outperform a 1D array in terms of contrast-to-noise and resolution, while also increasing the usable field-of-view, and that further studies encompassing the effects of scatter will be needed to optimize such systems.}, booktitle={2006 ieee nuclear science symposium conference record, vol 1-6}, author={Lalush, D. and Rajaram, R. and Quan, E. Z. and Zhang, J. A. and Lu, J. P. and Zhou, O. T.}, year={2006}, pages={1670–1673} }
 @article{zhang_cheng_lee_gao_qiu_lin_lalush_lu_zhou_2005, title={A nanotube-based field emission x-ray source for microcomputed tomography}, volume={76}, ISSN={0034-6748 1089-7623}, url={http://dx.doi.org/10.1063/1.2041589}, DOI={10.1063/1.2041589}, abstractNote={Microcomputed tomography (micro-CT) is a noninvasive imaging tool commonly used to probe the internal structures of small animals for biomedical research and for the inspection of microelectronics. Here we report the development of a micro-CT scanner with a carbon nanotube- (CNT-) based microfocus x-ray source. The performance of the CNT x-ray source and the imaging capability of the micro-CT scanner were characterized.}, number={9}, journal={Review of Scientific Instruments}, publisher={AIP Publishing}, author={Zhang, J. and Cheng, Y. and Lee, Y. Z. and Gao, B. and Qiu, Q. and Lin, W. L. and Lalush, D. and Lu, J. P. and Zhou, O.}, year={2005}, month={Sep}, pages={094301} }
 @article{lalush_jatko_segars_2005, title={An observer study methodology for evaluating detection of motion abnormalities in gated myocardial perfusion SPECT}, volume={52}, ISSN={["0018-9294"]}, DOI={10.1109/TBME.2004.843290}, abstractNote={To address the task of detecting nonischemic motion abnormalities from animated displays of gated myocardial perfusion single photon emission computed tomography data, we performed an observer study to evaluate the difference in detection performance between gating to 8 and 16 frames. Images were created from the NCAT mathematical phantom with a realistic heart simulating hypokinetic motion in the left lateral wall. Realistic noise-free projection data were simulated for both normal and defective hearts to obtain 16 frames for the cardiac cycle. Poisson noise was then simulated for each frame to create 50 realizations of each heart. All datasets were processed in two ways: reconstructed as a 16-frame set, and collapsed to 8 frames and reconstructed. Ten observers viewed the cardiac images animated with a realistic real-time frame rate. Observers trained on 100 images and tested on 100 images, rating their confidence on the presence of a motion defect on a continuous scale. None of the observers showed a significant difference in performance between the two gating methods. The 95% confidence interval on the difference in areas under the ROC curve (Az/sub 8/-Az/sub 16/) was -0.029-0.085. Our test did not find a significant difference in detection performance between 8-frame gating and 16-frame gating. We conclude that, for the task of detecting abnormal motion, increasing the number of gated frames from 8 to 16 offers no apparent advantage.}, number={3}, journal={IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING}, author={Lalush, DS and Jatko, MK and Segars, WP}, year={2005}, month={Mar}, pages={480–485} }
 @article{wang_tsui_lalush_tocharoenchai_frey_2005, title={Optimization of acquisition parameters for simultaneous Tl-201 and Tc-99m dual-isotope myocardial imaging}, volume={52}, ISSN={["1558-1578"]}, DOI={10.1109/TNS.2005.851421}, abstractNote={In /sup 201/Tl//sup 99m/Tc dual-isotope simultaneous-acquisition (DISA) myocardial imaging, crosstalk due to Tc photons results in significant contamination of the Tl data. The objective of this work is to seek the acquisition parameters (i.e., energy window width and center) that have the optimal tradeoff between minimizing the crosstalk and maximizing the detection efficiency. The optimization criterion was based on maximizing an ideal observer signal-to-noise ratio (SNR) for the myocardial defect detection task using single-isotope and DISA projection images acquired from a torso phantom. For single-isotope images, the optimal energy windows (width/center: 26 keV/75 keV and 28 keV/165 keV for /sup 201/Tl, 30 keV/142 keV for /sup 99m/Tc) are wider than typical windows. For DISA imaging, the optimal windows varied with the /sup 99m/Tc to /sup 201/Tl activity ratio and are thus likely to depend on the uptake ratio in each patient. Using the optimal ratio 2.25-2.75 (148 MBq /sup 201/Tl and 333-407 MBq /sup 99m/Tc) with the corresponding optimal windows (22 keV/72 keV, 24 keV/167 keV, and 24 keV/140 keV) gives /sup 201/Tl images with substantially increased SNRs as well as /sup 99m/Tc images with SNRs same as those of 370 MBq /sup 99m/Tc-only images. However, without the addition of crosstalk compensation, the use of the optimal activity and energy windows alone is likely not sufficient to restore the DISA Tl SNR to that of Tl-only image.}, number={5}, journal={IEEE TRANSACTIONS ON NUCLEAR SCIENCE}, author={Wang, WT and Tsui, BMW and Lalush, DS and Tocharoenchai, C and Frey, EC}, year={2005}, month={Oct}, pages={1227–1235} }
 @article{lalush_dimeo_2002, title={An observer study evaluating dual-plane circular-orbit cone- beam brain SPECT}, volume={43}, number={11}, journal={Journal of Nuclear Medicine}, author={Lalush, D. S. and Dimeo, A. J.}, year={2002}, pages={1578–1583} }