Purpose To examine heterogeneous breast cancer through intravoxel incoherent motion (IVIM) histogram analysis. Materials and methods This HIPAA-compliant, IRB-approved retrospective study included 62 patients (age 48.44±11.14 years, 50 malignant lesions and 12 benign) who underwent contrast-enhanced 3 T breast MRI and diffusion-weighted imaging. Apparent diffusion coefficient (ADC) and IVIM biomarkers of tissue diffusivity (Dt), perfusion fraction (fp), and pseudo-diffusivity (Dp) were calculated using voxel-based analysis for the whole lesion volume. Histogram analysis was performed to quantify tumour heterogeneity. Comparisons were made using Mann–Whitney tests between benign/malignant status, histological subtype, and molecular prognostic factor status while Spearman’s rank correlation was used to characterize the association between imaging biomarkers and prognostic factor expression. Results The average values of the ADC and IVIM biomarkers, Dt and fp, showed significant differences between benign and malignant lesions. Additional significant differences were found in the histogram parameters among tumour subtypes and molecular prognostic factor status. IVIM histogram metrics, particularly fp and Dp, showed significant correlation with hormonal factor expression. Conclusion Advanced diffusion imaging biomarkers show relationships with molecular prognostic factors and breast cancer malignancy. This analysis reveals novel diagnostic metrics that may explain some of the observed variability in treatment response among breast cancer patients.

Purpose To compare fitting methods and sampling strategies, including the implementation of an optimized b-value selection for improved estimation of intravoxel incoherent motion (IVIM) parameters in breast cancer. Methods Fourteen patients (age, 48.4 ± 14.27 years) with cancerous lesions underwent 3 Tesla breast MRI examination for a HIPAA-compliant, institutional review board approved diffusion MR study. IVIM biomarkers were calculated using “free” versus “segmented” fitting for conventional or optimized (repetitions of key b-values) b-value selection. Monte Carlo simulations were performed over a range of IVIM parameters to evaluate methods of analysis. Relative bias values, relative error, and coefficients of variation (CV) were obtained for assessment of methods. Statistical paired t-tests were used for comparison of experimental mean values and errors from each fitting and sampling method. Results Comparison of the different analysis/sampling methods in simulations and experiments showed that the “segmented” analysis and the optimized method have higher precision and accuracy, in general, compared with “free” fitting of conventional sampling when considering all parameters. Regarding relative bias, IVIM parameters fp and Dt differed significantly between “segmented” and “free” fitting methods. Conclusion: IVIM analysis may improve using optimized selection and “segmented” analysis, potentially enabling better differentiation of breast cancer subtypes and monitoring of treatment.

Purpose To collect diffusion tensor imaging (DTI) at multiple diffusion times Td in skeletal muscle in normal subjects and chronic exertional compartment syndrome (CECS) patients and analyze the data with the random permeable barrier model (RPBM) for biophysical specificity. Materials and Methods Using an IRB-approved HIPAA-compliant protocol, seven patients with clinical suspicion of CECS and eight healthy volunteers underwent DTI of the calf muscle in a Siemens MAGNETOM Verio 3-T scanner at rest and after treadmill exertion at 4 different diffusion times. Radial diffusion values λrad were computed for each of 7 different muscle compartments and analyzed with RPBM to produce estimates of free diffusivity D0, fiber diameter a, and permeability κ. Fiber diameter estimates were compared with measurements from literature autopsy reference for several compartments. Response factors (post/pre-exercise ratios) were computed and compared between normal controls and CECS patients using a mixed-model two-way analysis of variance. Results All subjects and muscle compartments showed nearly time-independent diffusion along and strongly time-dependent diffusion transverse to the muscle fibers. RPBM estimates of fiber diameter correlated well with corresponding autopsy reference. D0 showed significant (p<0.05) increases with exercise for volunteers, and a increased significantly (p<0.05) in volunteers. At the group level, response factors of all three parameters showed trends differentiating controls from CECS patients, with patients showing smaller diameter changes (p=0.07), and larger permeability increases (p=0.07) than controls. Conclusions Time-dependent diffusion measurements combined with appropriate tissue modeling can provide enhanced microstructural specificity for in vivo tissue characterization. In CECS patients, our results suggest that high-pressure interfiber edema elevates free diffusion and restricts exercise-induced fiber dilation. Such specificity may be useful in differentiating CECS from other disorders or in predicting its response to either physical therapy or fasciotomy.

A mechanistic understanding of the pathology of psychiatric disorders has been hampered by extensive heterogeneity in biology, symptoms, and behavior within diagnostic categories that are defined subjectively. We investigated whether leveraging individual differences in information-processing impairments in patients with post-traumatic stress disorder (PTSD) could reveal phenotypes within the disorder. We found that a subgroup of patients with PTSD from two independent cohorts displayed both aberrant functional connectivity within the ventral attention network (VAN) as revealed by functional magnetic resonance imaging (fMRI) neuroimaging and impaired verbal memory on a word list learning task. This combined phenotype was not associated with differences in symptoms or comorbidities, but nonetheless could be used to predict a poor response to psychotherapy, the best-validated treatment for PTSD. Using concurrent focal noninvasive transcranial magnetic stimulation and electroencephalography, we then identified alterations in neural signal flow in the VAN that were evoked by direct stimulation of that network. These alterations were associated with individual differences in functional fMRI connectivity within the VAN. Our findings define specific neurobiological mechanisms in a subgroup of patients with PTSD that could contribute to the poor response to psychotherapy.