Faculty Bibliography

Clinically isolated syndrome (CIS) is a central nervous system inflammatory and demyelinating event that lasts at least 24 h and can represent the first episode of relapsing-remitting multiple sclerosis. MRI is an important imaging tool in the diagnosis and longitudinal monitoring of CIS progression. Accurate differential diagnosis of high-risk versus low-risk CIS is important because high-risk CIS patients could be treated early. Although a few studies have previously characterized CIS and explored possible imaging predictors of CIS conversion to MS, it remains unclear which amongst the commonly measured MRI features, if any, are good predictors of rapid disease progression in CIS patients. The goal of this review paper is to identify MRI features in high-risk CIS patients that are associated with rapid disease activity within 5 years as measured by clinical disability.

Radiologically isolated syndrome (RIS) is the asymptomatic precursor to clinically isolated syndrome, relapsing-remitting multiple sclerosis (MS) or primary progressive MS. RIS is frequently diagnosed when an individual gets an MRI for an unrelated medical issue, such as headache or trauma. Treating RIS patients is controversial, but physicians may be inclined to offer prophylactic treatment for high-risk RIS patients. Identifying imaging and clinical features associated with high likelihood of early clinical conversion may prove helpful to identify a high-risk subset for potential MS therapy. The goal of this paper is to review current literatures to identify imaging and clinical features that predict early (within 5 years) conversion from RIS to MS.

PURPOSE/OBJECTIVE:To investigate gray-matter (GM) lesions in relapsing-remitting multiple sclerosis (MS) using double-inversion recovery (DIR) MRI, determine GM lesions prevalence, spatial distribution and characterize their contrast-enhancement, diffusion characteristics and compare them to white-matter (WM) lesions. This is the first study, to our knowledge, to investigate GM MS lesions using double-inversion recovery MRI, to determine GM lesion prevalence and location, and characterize contrast-enhancement and diffusion characteristics, compared to WM lesion characteristics in the same patients. We also correlated GM lesion counts, volume and apparent diffusion coefficient (ADC) with total brain, WM, and GM volumes, as well as 25-foot walk test as a clinical disability. MATERIALS AND METHODS/METHODS:This retrospective study included 44 relapsing-remitting MS patients (12M/32F, 41 ± 13 years) and 24 age-matched healthy controls (14M/10F, 36 ± 13 years). Lesions were segmented based on DIR and grouped into GM, subcortical WM, and periventricular WM lesions. ADC was tabulated for contrast-enhancing and non-enhancing lesions. Unpaired two sample t-tests were used for comparison between groups. Linear regression was used to evaluate the relationship between number of GM lesions, number of total lesions, total GM lesion volume, and total WM lesion volume with brain volumes and clinical data. RESULTS:GM MS lesions were present in the majority (86.4%, 38/44) of RRMS patients based on DIR, suggesting GM damage plays an important role in MS pathogenesis. The majority of the GM lesions were located in the frontal lobe. The percentage of lesions in GM that were contrast-enhanced was similar to those in WM, suggesting that blood-brain barrier integrity is likely affected similarly in GM and WM. Contrast-enhanced GM lesions showed higher ADC. GM lesion count and volume were correlated with global and regional brain atrophy, and with more severe disability group. CONCLUSION/CONCLUSIONS:This study characterized GM MS lesions using double-inversion recovery, contrast-enhanced and diffusion MRI. Understanding GM lesion pathophysiology using MRI in vivo, may prove useful for improving targeted therapy and monitoring disease progression.

Conventional radiation therapy of brain tumors often produces cognitive deficits, particularly in children. We investigated the potential efficacy of merging Orthovoltage X-ray Minibeams (OXM). It segments the beam into an array of parallel, thin (~0.3 mm), planar beams, called minibeams, which are known from synchrotron x-ray experiments to spare tissues. Furthermore, the slight divergence of the OXM array make the individual minibeams gradually broaden, thus merging with their neighbors at a given tissue depth to produce a solid beam. In this way the proximal tissues, including the cerebral cortex, can be spared. Here we present experimental results with radiochromic films to characterize the method's dosimetry. Furthermore, we present our Monte Carlo simulation results for physical absorbed dose, and a first-order biologic model to predict tissue tolerance. In particular, a 220-kVp orthovoltage beam provides a 5-fold sharper lateral penumbra than a 6-MV x-ray beam. The method can be implemented in arc-scan, which may include volumetric-modulated arc therapy (VMAT). Finally, OXM's low beam energy makes it ideal for tumor-dose enhancement with contrast agents such as iodine or gold nanoparticles, and its low cost, portability, and small room-shielding requirements make it ideal for use in the low-and-middle-income countries.

This work proposes a novel MRI method - Intrinsic Diffusivity Encoding of Arterial Labeled Spin (IDEALS) - for the whole-brain mapping of water permeability in the human brain without an exogenous contrast agent. Quantitative separation of the intravascular and extravascular labeled water MRI signal was achieved in arterial spin labeling experiments with segmented 3D-GRASE acquisition by modulating the relative sensitivity between relaxation, true diffusion, and pseudodiffusion. The intrinsic diffusivity encoding in k-space created different broadening of the image-domain point spread functions for intravascular and extravascular labeled spins, from which blood-brain barrier (BBB) water extraction fraction (E_w) and water permeability surface area product (PS_w) were estimated. The feasibility and sensitivity of this method was evaluated in healthy subjects at baseline and after caffeine challenge. The estimated baseline E_w and PS_w maps showed contrast among gray matter (GM) and white matter (WM). GM E_w was significantly lower than that of WM (78.8% ± 3.3% in GM vs. 83.9% ± 4.6% in WM; p < 0.05) and GM PS_w was significantly higher than that of WM (131.7 ± 29.5 mL/100  g/min in GM vs. 76.2 ± 18.4 mL/100  g/min in WM; p < 0.05). BBB E_w was significantly lower for females than males (74.9% ± 3.7% for females vs. 81.3% ± 3.3% for males in GM; 80.5% ± 4.7% for females vs. 86.1 ± 3.0 for males in WM; p < 0.05 for both), while significant PS_w differences were only observed in WM (143.8 ± 34.4 mL/100  g/min for females vs. 123.6 ± 24.4 mL/100  g/min for males in GM; 91.6 ± 15.0 mL/100  g/min for females vs. 65.9 ± 12.5 mL/100  g/min for males in WM; p = 0.20 and p < 0.05 for GM and WM respectively). Significant correlations between E_w and CBF (r = -0.32, p < 0.05) and between PS_w and CBF (r = 0.89, p < 0.05) were observed, consistent with ¹⁵O-H₂O PET findings. After caffeine challenge, reduced CBF, E_w and PS_w were observed, demonstrating the sensitivity of IDEALS approach.

OBJECTIVE:FDG PET/MRI examination of the body is routinely performed from the skull base to the mid thigh. Many types of brain abnormalities potentially could be detected on PET/MRI if the head was included. The objective of this study was therefore to identify and characterize brain findings incidentally detected on PET/MRI of the body with the head included. MATERIALS AND METHODS/METHODS:We retrospectively identified 269 patients with FDG PET/MRI whole-body scans that included the head. PET/MR images of the brain were reviewed by a nuclear medicine physician and neuroradiologist, first individually and then concurrently. Both PET and MRI findings were identified, including abnormal FDG uptake, standardized uptake value, lesion size, and MRI signal characteristics. For each patient, relevant medical history and prior imaging were reviewed. RESULTS:Of the 269 subjects, 173 were women and 96 were men (mean age, 57.4 years). Only the initial PET/MR image of each patient was reviewed. A total of 37 of the 269 patients (13.8%) had abnormal brain findings noted on the PET/MRI whole-body scan. Sixteen patients (5.9%) had vascular disease, nine patients (3.3%) had posttherapy changes, and two (0.7%) had benign cystic lesions in the brain. Twelve patients (4.5%) had serious nonvascular brain abnormalities, including cerebral metastasis in five patients and pituitary adenomas in two patients. Only nine subjects (3.3%) had a new neurologic or cognitive symptom suggestive of a brain abnormality. CONCLUSION/CONCLUSIONS:Routine body imaging with FDG PET/MRI of the area from the skull base to the mid thigh may miss important brain abnormalities when the head is not included. The additional brain abnormalities identified on whole-body imaging may provide added clinical value to the management of oncology patients.