Faculty Bibliography

We seek to elucidate the underlying pathophysiology of injury sustained after mild traumatic brain injury (MTBI) using multi-shell diffusion MRI, deriving compartment-specific WM tract integrity (WMTI) metrics. WMTI allows a more biophysical interpretation of WM changes by describing microstructural characteristics in both intra- and extra-axonal environments. Thirty-two patients with MTBI within 30 days of injury and twenty-one age- and sex-matched controls were imaged on a 3T MR scanner. Multi-shell diffusion acquisition was performed with 5 b-values (250 - 2500 s/mm²) along 6 - 60 diffusion encoding directions. Tract-based spatial statistics (TBSS) was used with family-wise error (FWE) correction for multiple comparisons. TBSS results demonstrate focally lower intra-axonal diffusivity (D_axon) in MTBI patients in the splenium of the corpus callosum (sCC) (p < 0.05, FWE-corrected). The Area Under the Curve (AUC)-value for was 0.76 with low sensitivity of 46.9%, but 100% specificity. These results indicate that D_axon may be a useful imaging biomarker highly specific for MTBI-related WM injury. The observed decrease in D_axon suggests restriction of the diffusion along the axons occurring shortly after injury.

Remarkable advances have been made in the last decade in the use of diffusion MR imaging to study mild traumatic brain injury (mTBI). Diffusion imaging shows differences between mTBI patients and healthy control groups in multiple different metrics using a variety of techniques, supporting the notion that there are microstructural injuries in mTBI patients that radiologists have been insensitive to. Future areas of discovery in diffusion MR imaging and mTBI include larger longitudinal studies to better understand the evolution of the injury and unravel the biophysical meaning that the detected changes in diffusion MR imaging represent.

Objective: Report initial results from the Multiple Sclerosis Partners Advancing Technology and Health Solutions (MS PATHS) project. Background: The Learning Health System (LHS) concept involves collecting standardized clinical and imaging data during the course of patient care. The data would then serve two purposes simultaneously: data-driven clinical care decisions and systematic learning. Design/Methods: MS PATHS was designed around the LHS concept, through collaborative meetings in 2015-2016. MS PATHS participants self-administer the Multiple Sclerosis Performance Test (MSPT) at routine clinical visits. MSPT is an iPad-based medical device designed and validated for MS. MSPT includes components of the MSFC-4, NeuroQoL, and a standardized MS history. For imaging data, brain MRIs are acquired on 3T Siemens scanners using identical image acquisition parameters, to allow generation of highly standardized MRI-metrics. Participants may also elect to contribute to a biorepository. Results: As of Oct 19, 2016, seven US centers were participating in MS PATHS in collaboration with Biogen, under guidance of a steering committee of 3 neurologists and 1 neuroradiologist from participating centers and a Biogen representative. From May 17, 2016 through October 19, 2016, 1507 patients with MS were enrolled in MS PATHS, 317 with two or more visits. Data from 1127 MSPT assessments are currently available in the LHS database, 342 with brain MRIs. Opt-in rate for data sharing has exceeded 90%, suggesting the study will yield a representative population from participating centers. Across patients currently enrolled (mean+- SD): age=52+/-12 years, Walking Speed Test = 8.46 +/- 5.54 sec, and Dominant Hand Manual Dexterity Test = 28.3 +/- 7.7 sec. Updated results and lessons learned will be presented. Conclusions: MS PATHS is the first LHS established in MS. Enrollment has been rapid, and patient acceptance high. Standardized, comprehensive clinical and imaging data collection will accelerate collaborative research efforts and support data-driven patient management

Objective: To design and implement a strategy to enable high quality, standardized MRI acquisitions across a network of participating healthcare institutions (MS PATHS). Background: Although imaging guidelines for MS patients have been recommended and MRI protocols are specified for clinical trials, there remains a high degree of variability in acquisition parameters that limit the reliability of quantitative measurements. As part of MS PATHS, we are collaborating with a network of MS centers to standardize the acquisition of MRI images for quantitative analysis. Our goal is to test the feasibility and clinical utility of collecting research-quality MRI data during routine clinical care. Design/Methods: A standardized MRI protocol was designed by healthcare institution neuroradiologists and imaging scientists at Biogen and Siemens to be feasible for routine use for multicenter imaging of any MS patient referred for MRI, and optimized for automated quantitative analysis of brain volume and MS lesions. Incorporation of these agreed-upon sequences into the routine MS-MRI protocol was part of the MS PATHS start-up process. Results: The MS PATHS brain imaging protocol includes two 1mm isotropic product sequences optimized for Siemens 3T scanners: a pre-contrast 3D MPRAGE and 3D SPACE FLAIR with a total scan time of 11.42 minutes. Currently, the highly standardized sequences have been implemented as standard of care in 8 institutions. Within the first 2 weeks since activation, 383 retrospective MRI studies from 342 unique patients were received from the first institution and 98.5% of these scans passed automated QA/QC, demonstrating the initial feasibility of this approach. Conclusions: To our knowledge this is the first implementation of a rigorously standardized MRI protocol across MS centers to generate research quality imaging metrics in clinical practice. Integration into a learning health system will improve clinical care and research

Diffusion imaging of the spine has the potential to change clinical management, but is challenging due to the small size of the cord and susceptibility artifacts from adjacent structures. Reduced field-of-view (rFOV) diffusion can improve image quality by decreasing the echo train length. Over the past 2 years, we have acquired a rFOV diffusion sequence for MRI spine protocols on most inpatients and emergency room patients. We provide selected imaging diagnoses to illustrate the utility of including diffusion spine MRI in clinical practice. Our experiences support using diffusion MRI to improve diagnostic certainty and facilitate prompt treatment or clinical management.

While cerebral amyloid angiopathy is a common cause of lobar hemorrhage, rarely it may be associated with an inflammatory response, thought to be incited by amyloid deposits. We report a 73-year-old woman with an extensive cancer history who presented with tumor-like lesions and symptoms of homonymous hemianopia and prosopagnosia. Found to have cerebral amyloid angiopathy-related inflammation proven by brain biopsy, she was treated successfully with immunosuppression.

Saccades rapidly direct the line of sight to targets of interest to make use of the high acuity foveal region of the retina. These fast eye movements are instrumental for scanning visual scenes, foveating targets, and, ultimately, serve to guide manual motor control, including eye-hand coordination. Cerebral injury has long been known to impair ocular motor control. Recently, it has been suggested that alterations in control may be useful as a marker for recovery. We measured eye movement control in a saccade task in subjects with chronic middle cerebral artery stroke with both cortical and substantial basal ganglia involvement and in healthy controls. Saccade latency distributions were bimodal, with an early peak at 60 ms (anticipatory saccades) and a later peak at 250 ms (regular saccades). Although the latencies corresponding to these peaks were the same in the two groups, there were clear differences in the size of the peaks. Classifying saccade latencies relative to the saccade "go signal" into anticipatory (latencies up to 80 ms), "early" (latencies between 80 and 160 ms), and "regular" types (latencies longer than 160 ms), stroke subjects displayed a disproportionate number of anticipatory saccades, whereas control subjects produced the majority of their saccades in the regular range. We suggest that this increase in the number of anticipatory saccade events may result from a disinhibition phenomenon that manifests as an impairment in the endogenous control of ocular motor events (saccades) and interleaved fixations. These preliminary findings may help shed light on the ocular motor deficits of neurodegenerative conditions, results that may be subclinical to an examiner, but clinically significant secondary to their functional implications.

The effect of T1 signal on FSL voxel-based morphometry modulated GM density and FreeSurfer cortical thickness is explored. The techniques rely on different analyses, but both are commonly used to detect spatial changes in GM. Standard pipelines show FSL voxel-based morphometry is sensitive to T1 signal alterations within a physiologic range, and results can appear discordant between FSL voxel-based morphometry and FreeSurfer cortical thickness. Care should be taken in extrapolating results to the effect on brain volume.