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MRI assessment of the thigh musculature in dermatomyositis and healthy subjects using diffusion tensor imaging, intravoxel incoherent motion and dynamic DTI

Sigmund, E E; Baete, S H; Luo, T; Patel, K; Wang, D; Rossi, I; Duarte, A; Bruno, M; Mossa, D; Femia, A; Ramachandran, S; Stoffel, D; Babb, J S; Franks, A; Bencardino, J
INTRODUCTION/BACKGROUND:Dermatomyositis (DM) is an idiopathic inflammatory myopathy involving severe debilitation in need of diagnostics. We evaluated the proximal lower extremity musculature with diffusion tensor imaging (DTI), intravoxel incoherent motion (IVIM) and dynamic DTI in DM patients and controls and compared with standard clinical workup.  METHODS: In this IRB-approved, HIPAA-compliant study with written informed consent, anatomical, Dixon fat/water and diffusion imaging were collected in bilateral thigh MRI of 22 controls and 27 DM patients in a 3T scanner. Compartments were scored on T1/T2 scales. Single voxel dynamic DTI metrics in quadriceps before and after 3-min leg exercise were measured. Spearman rank correlation and mixed model analysis of variance/covariance (ANOVA/ANCOVA) were used to correlate with T1 and T2 scores and to compare patients with controls. RESULTS:DM patients showed significantly lower pseudo-diffusion and volume in quadriceps than controls. All subjects showed significant correlation between T1 score and signal-weighted fat fraction; tissue diffusion and pseudo-diffusion varied significantly with T1 and T2 score in patients. Radial and mean diffusion exercise response in patients was significantly higher than controls. CONCLUSION/CONCLUSIONS:Static and dynamic diffusion imaging metrics show correlation with conventional imaging scores, reveal spatial heterogeneity, and provide means to differentiate dermatomyositis patients from controls. KEY POINTS/CONCLUSIONS:• Diffusion imaging shows regional differences between thigh muscles of dermatomyositis patients and controls. • Signal-weighted fat fraction and diffusion metrics correlate with T1/T2 scores of disease severity. • Dermatomyositis patients show significantly higher radial diffusion exercise response than controls.
PMID: 29869178
ISSN: 1432-1084
CID: 3144442

Spatially resolved kinetics of skeletal muscle exercise response and recovery with multiple echo diffusion tensor imaging (MEDITI): a feasibility study

Sigmund, E E; Baete, S H; Patel, K; Wang, D; Stoffel, D; Otazo, R; Parasoglou, P; Bencardino, J
OBJECTIVES/OBJECTIVE:We describe measurement of skeletal muscle kinetics with multiple echo diffusion tensor imaging (MEDITI). This approach allows characterization of the microstructural dynamics in healthy and pathologic muscle. MATERIALS AND METHODS/METHODS:In a Siemens 3-T Skyra scanner, MEDITI was used to collect dynamic DTI with a combination of rapid diffusion encoding, radial imaging, and compressed sensing reconstruction in a multi-compartment agarose gel rotation phantom and within in vivo calf muscle. An MR-compatible ergometer (Ergospect Trispect) was employed to enable in-scanner plantar flexion exercise. In a HIPAA-compliant study with written informed consent, post-exercise recovery of DTI metrics was quantified in eight volunteers. Exercise response of DTI metrics was compared with that of T2-weighted imaging and characterized by a gamma variate model. RESULTS: = 0.303 ± 0.185). Diffusion and T2-weighted response magnitudes were correlated (e.g., r = 0.792, p = 0.019 for nMD vs. nT2w). CONCLUSION/CONCLUSIONS:We have demonstrated the feasibility of MEDITI for capturing spatially resolved diffusion tensor data in dynamic systems including post-exercise skeletal muscle recovery following in-scanner plantar flexion.
PMID: 29761414
ISSN: 1352-8661
CID: 3121362

REnal Flow and Microstructure AnisotroPy (REFMAP) MRI in Normal and Peritumoral Renal Tissue

Liu, Andrea L; Mikheev, Artem; Rusinek, Henry; Huang, William C; Wysock, James S; Babb, James S; Feiweier, Thorsten; Stoffel, David; Chandarana, Hersh; Sigmund, Eric E
BACKGROUND:Diffusion-weighted imaging (DWI) provides insight into the pathophysiology underlying renal dysfunction. Variants of DWI include intravoxel incoherent motion (IVIM), which differentiates between microstructural diffusion and vascular or tubular flow, and diffusion tensor imaging (DTI), which quantifies diffusion directionality. PURPOSE/OBJECTIVE:To investigate the reproducibility of joint IVIM-DTI and compare controls to presurgical renal mass patients. STUDY TYPE/METHODS:Prospective cross-sectional. SUBJECTS/METHODS:Thirteen healthy controls and ten presurgical renal mass patients were scanned. Ten controls were scanned twice to investigate reproducibility. FIELD STRENGTH/SEQUENCE/UNASSIGNED:Subjects were scanned on a 3T system using 10 b-values and 20 diffusion directions for IVIM-DTI in a study approved by the local Institutional Review Board. ASSESSMENT/RESULTS:Retrospective coregistration and measurement of joint IVIM-DTI parameters were performed. STATISTICAL ANALYSIS/METHODS:Parameter reproducibility was defined as intraclass correlation coefficient (ICC) >0.7 and coefficient of variation (CV) <30%. Patient data were stratified by lesion side (contralateral/ipsilateral) for comparison with controls. Corticomedullary differentiation was evaluated. RESULTS:In controls, the reproducible subset of REnal Flow and Microstructure AnisotroPy (REFMAP) parameters had average ICC = 0.82 and CV = 7.5%. In renal mass patients, medullary fractional anisotropy (FA) was significantly lower than in controls (0.227 ± 0.072 vs. 0.291 ± 0.044, P = 0.016 for the kidney contralateral to the mass and 0.228 ± 0.070 vs. 0.291 ± 0.044, P = 0.018 for the kidney ipsilateral). In the kidney ipsilateral to the mass, cortical Dp,radial was significantly higher than in controls (P = 0.012). Conversely, medullary Dp,axial was significantly lower in contralateral than ipsilateral kidneys (P = 0.027) and normal controls (P = 0.044). DATA CONCLUSION/UNASSIGNED:REFMAP-MRI parameters provide unique information regarding renal dysfunction. In presurgical renal mass patients, directional flow changes were noted that were not identified with IVIM analysis alone. Both contralateral and ipsilateral kidneys in patients show reductions in structural diffusivities and anisotropy, while flow metrics showed opposing changes in contralateral vs. ipsilateral kidneys. LEVEL OF EVIDENCE/METHODS:2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
PMCID:6030440
PMID: 29331053
ISSN: 1522-2586
CID: 2906262

Voxelwise analysis of simultaneously acquired and spatially correlated 18 F-fluorodeoxyglucose (FDG)-PET and intravoxel incoherent motion metrics in breast cancer

Ostenson, Jason; Pujara, Akshat C; Mikheev, Artem; Moy, Linda; Kim, Sungheon G; Melsaether, Amy N; Jhaveri, Komal; Adams, Sylvia; Faul, David; Glielmi, Christopher; Geppert, Christian; Feiweier, Thorsten; Jackson, Kimberly; Cho, Gene Y; Boada, Fernando E; Sigmund, Eric E
PURPOSE: Diffusion-weighted imaging (DWI) and 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET) independently correlate with malignancy in breast cancer, but the relationship between their structural and metabolic metrics is not completely understood. This study spatially correlates diffusion, perfusion, and glucose avidity in breast cancer with simultaneous PET/MR imaging and compares correlations with clinical prognostics. METHODS: In this Health Insurance Portability and Accountability Act-compliant prospective study, with written informed consent and approval of the institutional review board and using simultaneously acquired FDG-PET and DWI, tissue diffusion (Dt ), and perfusion fraction (fp ) from intravoxel incoherent motion (IVIM) analysis were registered to FDG-PET within 14 locally advanced breast cancers. Lesions were analyzed using 2D histograms and correlation coefficients between Dt , fp , and standardized uptake value (SUV). Correlations were compared with prognostics from biopsy, metastatic burden from whole-body PET, and treatment history. RESULTS: SUV||Dt correlation coefficient significantly distinguished treated (0.11 +/- 0.24) from nontreated (-0.33 +/- 0.26) patients (P = 0.005). SUV||fp correlations were on average negative for the whole cohort (-0.17 +/- 0.13). CONCLUSION: Simultaneously acquired and registered FDG-PET/DWI allowed quantifiable descriptions of breast cancer microenvironments that may provide a framework for monitoring and predicting response to treatment. Magn Reson Med, 2016. (c) 2016 International Society for Magnetic Resonance in Medicine.
PMCID:5405014
PMID: 27779790
ISSN: 1522-2594
CID: 2288692

In vivo measurement of membrane permeability and myofiber size in human muscle using time-dependent diffusion tensor imaging and the random permeable barrier model

Fieremans, Els; Lemberskiy, Gregory; Veraart, Jelle; Sigmund, Eric E; Gyftopoulos, Soterios; Novikov, Dmitry S
The time dependence of the diffusion coefficient is a hallmark of tissue complexity at the micrometer level. Here we demonstrate how biophysical modeling, combined with a specifically tailored diffusion MRI acquisition performing diffusion tensor imaging (DTI) for varying diffusion times, can be used to determine fiber size and membrane permeability of muscle fibers in vivo. We describe the random permeable barrier model (RPBM) and its assumptions, as well as the details of stimulated echo DTI acquisition, signal processing steps, and potential pitfalls. We illustrate the RPBM method on a few pilot examples involving human subjects (previously published as well as new), such as revealing myofiber size derived from RPBM increase after training in a calf muscle, and size decrease with atrophy in shoulder rotator cuff muscle. Finally, we comment on the potential clinical relevance of our results
PMID: 27717099
ISSN: 1099-1492
CID: 2274332

Diffusion-weighted breast MRI: Clinical applications and emerging techniques

Partridge, Savannah C; Nissan, Noam; Rahbar, Habib; Kitsch, Averi E; Sigmund, Eric E
Diffusion-weighted MRI (DWI) holds potential to improve the detection and biological characterization of breast cancer. DWI is increasingly being incorporated into breast MRI protocols to address some of the shortcomings of routine clinical breast MRI. Potential benefits include improved differentiation of benign and malignant breast lesions, assessment and prediction of therapeutic efficacy, and noncontrast detection of breast cancer. The breast presents a unique imaging environment with significant physiologic and inter-subject variations, as well as specific challenges to achieving reliable high quality diffusion-weighted MR images. Technical innovations are helping to overcome many of the image quality issues that have limited widespread use of DWI for breast imaging. Advanced modeling approaches to further characterize tissue perfusion, complexity, and glandular organization may expand knowledge and yield improved diagnostic tools. LEVEL OF EVIDENCE: 5 J. Magn. Reson. Imaging 2016.
PMCID:5222835
PMID: 27690173
ISSN: 1522-2586
CID: 2262822

Stimulated echo diffusion tensor imaging (STEAM-DTI) with varying diffusion times as a probe of breast tissue

Teruel, Jose R; Cho, Gene Y; Moccaldi Rt, Melanie; Goa, Pal E; Bathen, Tone F; Feiweier, Thorsten; Kim, Sungheon G; Moy, Linda; Sigmund, Eric E
PURPOSE: To explore the application of diffusion tensor imaging (DTI) for breast tissue and breast pathologies using a stimulated-echo acquisition mode (STEAM) with variable diffusion times. MATERIALS AND METHODS: In this Health Insurance Portability and Accountability Act-compliant study, approved by the local institutional review board, eight patients and six healthy volunteers underwent an MRI examination at 3 Tesla including STEAM-DTI with several diffusion times ranging from 68.5 to 902.5 ms. A DTI model was fitted to the data for each diffusion time, and parametric maps of mean diffusivity, fractional anisotropy, axial diffusivity, and radial diffusivity were computed for healthy fibroglandular tissue (FGT) and lesions. The median value of radial diffusivity for FGT was fitted to a linear decay to obtain an estimation of the surface-to-volume ratio, from which the radial diameter was calculated. RESULTS: For healthy FGT, radial diffusivity presented a linear decay with the square root of the diffusion time resulting in a range of estimated radial diameters from 202 to 496 microm, while axial diffusivity presented a nearly time-independent diffusion. Residual fat signal was reduced at longer diffusion times due to the shorter T1 of fat. Residual fat signal to the overall signal in the healthy volunteers' FGT was found to range from 2.39% to 2.55% (shortest mixing time), and from 0.40% to 0.51% (longest mixing time) for the b500 images. CONCLUSION: The use of variable diffusion times may provide an in vivo noninvasive tool to probe diffusion lengths in breast tissue and breast pathology, and might aid by improving fat suppression at longer diffusion times. J. Magn. Reson. Imaging 2016.
PMID: 27441890
ISSN: 1522-2586
CID: 2185552

Intravoxel incoherent motion (IVIM) histogram biomarkers for prediction of neoadjuvant treatment response in breast cancer patients

Cho, Gene Y; Gennaro, Lucas; Sutton, Elizabeth J; Zabor, Emily C; Zhang, Zhigang; Giri, Dilip; Moy, Linda; Sodickson, Daniel K; Morris, Elizabeth A; Sigmund, Eric E; Thakur, Sunitha B
OBJECTIVE: To examine the prognostic capabilities of intravoxel incoherent motion (IVIM) metrics and their ability to predict response to neoadjuvant treatment (NAT). Additionally, to observe changes in IVIM metrics between pre- and post-treatment MRI. METHODS: This IRB-approved, HIPAA-compliant retrospective study observed 31 breast cancer patients (32 lesions). Patients underwent standard bilateral breast MRI along with diffusion-weighted imaging before and after NAT. Six patients underwent an additional IVIM-MRI scan 12-14 weeks after initial scan and 2 cycles of treatment. In addition to apparent diffusion coefficients (ADC) from monoexponential decay, IVIM mean values (tissue diffusivity Dt, perfusion fraction fp, and pseudodiffusivity Dp) and histogram metrics were derived using a biexponential model. An additional filter identified voxels of highly vascular tumor tissue (VTT), excluding necrotic or normal tissue. Clinical data include histology of biopsy and clinical response to treatment through RECIST assessment. Comparisons of treatment response were made using Wilcoxon rank-sum tests. RESULTS: Average, kurtosis, and skewness of pseudodiffusion Dp significantly differentiated RECIST responders from nonresponders. ADC and Dt values generally increased ( approximately 70%) and VTT% values generally decreased ( approximately 20%) post-treatment. CONCLUSION: Dp metrics showed prognostic capabilities; slow and heterogeneous pseudodiffusion offer poor prognosis. Baseline ADC/Dt parameters were not significant predictors of response. This work suggests that IVIM mean values and heterogeneity metrics may have prognostic value in the setting of breast cancer NAT.
PMCID:5565789
PMID: 28856177
ISSN: 2352-0477
CID: 2678922

Comparison of Whole-Body F FDG PET/MR Imaging and Whole-Body F FDG PET/CT in Terms of Lesion Detection and Radiation Dose in Patients with Breast Cancer

Melsaether, Amy N; Raad, Roy A; Pujara, Akshat C; Ponzo, Fabio D; Pysarenko, Kristine M; Jhaveri, Komal; Babb, James S; Sigmund, Eric E; Kim, Sungheon G; Moy, Linda A
Purpose To compare fluorine 18 (18F) fluorodeoxyglucose (FDG) combined positron emission tomography (PET) and magnetic resonance (MR) imaging with 18F FDG combined PET and computed tomography (CT) in terms of organ-specific metastatic lesion detection and radiation dose in patients with breast cancer. Materials and Methods From July 2012 to October 2013, this institutional review board-approved HIPAA-compliant prospective study included 51 patients with breast cancer (50 women; mean age, 56 years; range, 32-76 years; one man; aged 70 years) who completed PET/MR imaging with diffusion-weighted and contrast material-enhanced sequences after unenhanced PET/CT. Written informed consent for study participation was obtained. Two independent readers for each modality recorded site and number of lesions. Imaging and clinical follow-up, with consensus in two cases, served as the reference standard. Results There were 242 distant metastatic lesions in 30 patients, 18 breast cancers in 17 patients, and 19 positive axillary nodes in eight patients. On a per-patient basis, PET/MR imaging with diffusion-weighted and contrast-enhanced sequences depicted distant (30 of 30 [100%] for readers 1 and 2) and axillary (eight of eight [100%] for reader 1, seven of eight [88%] for reader 2) metastatic disease at rates similar to those of unenhanced PET/CT (distant metastatic disease: 28 of 29 [96%] for readers 3 and 4, P = .50; axillary metastatic disease: seven of eight [88%] for readers 3 and 4, P > .99) and outperformed PET/CT in the detection of breast cancer (17 of 17 [100%] for readers 1 and 2 vs 11 of 17 [65%] for reader 3 and 10 of 17 [59%] for reader 4; P < .001). PET/MR imaging showed increased sensitivity for liver (40 of 40 [100%] for reader 1 and 32 of 40 [80%] for reader 2 vs 30 of 40 [75%] for reader 3 and 28 of 40 [70%] for reader 4; P < .001) and bone (105 of 107 [98%] for reader 1 and 102 of 107 [95%] for reader 2 vs 106 of 107 [99%] for reader 3 and 93 of 107 [87%] for reader 4; P = .012) metastases and revealed brain metastases in five of 51 (10%) patients. PET/CT trended toward increased sensitivity for lung metastases (20 of 23 [87%] for reader 1 and 17 of 23 [74%] for reader 2 vs 23 of 23 [100%] for reader 3 and 22 of 23 [96%] for reader 4; P = .065). Dose reduction averaged 50% (P < .001). Conclusion In patients with breast cancer, PET/MR imaging may yield better sensitivity for liver and possibly bone metastases but not for pulmonary metastases, as compared with that attained with PET/CT, at about half the radiation dose. (c) RSNA, 2016 Online supplemental material is available for this article.
PMCID:5028256
PMID: 27023002
ISSN: 1527-1315
CID: 2059122

Diffusion-weighted imaging outside the brain: Consensus statement from an ISMRM-sponsored workshop

Taouli, Bachir; Beer, Ambros J; Chenevert, Thomas; Collins, David; Lehman, Constance; Matos, Celso; Padhani, Anwar R; Rosenkrantz, Andrew B; Shukla-Dave, Amita; Sigmund, Eric; Tanenbaum, Lawrence; Thoeny, Harriet; Thomassin-Naggara, Isabelle; Barbieri, Sebastiano; Corcuera-Solano, Idoia; Orton, Matthew; Partridge, Savannah C; Koh, Dow-Mu
The significant advances in magnetic resonance imaging (MRI) hardware and software, sequence design, and postprocessing methods have made diffusion-weighted imaging (DWI) an important part of body MRI protocols and have fueled extensive research on quantitative diffusion outside the brain, particularly in the oncologic setting. In this review, we summarize the most up-to-date information on DWI acquisition and clinical applications outside the brain, as discussed in an ISMRM-sponsored symposium held in April 2015. We first introduce recent advances in acquisition, processing, and quality control; then review scientific evidence in major organ systems; and finally describe future directions. J. Magn. Reson. Imaging 2016.
PMCID:4983499
PMID: 26892827
ISSN: 1522-2586
CID: 1949892