Joseph Ross Mitchell

The clinical response to minocycline in multiple sclerosis is accompanied by beneficial immune changes: a pilot study

Minocycline has immunomodulatory and neuroprotective activities in vitro and in an animal model of multiple sclerosis (MS). We have previously reported that minocycline decreased gadolinium-enhancing activity over six months in a small trial of patients with active relapsing-remitting MS (RRMS). Here we report the impact of oral minocycline on clinical and magnetic resonance imaging (MRI) outcomes and serum immune molecules in this cohort over 24 months of open-label minocycline treatment. Despite a moderately high pretreatment annualized relapse rate (1.3/year pre-enrolment; 1.2/year during a three-month baseline period) prior to treatment, no relapses occurred between months 6 and 24. Also, despite very active MRI activity pretreatment (19/40 scans had gadolinium-enhancing activity during a three-month run-in), the only patient with gadolinium-enhancing lesions on MRI at 12 and 24 months was on half-dose minocycline. Levels of the p40 subunit of interleukin (IL)-12, which at high levels might antagonize the proinflammatory IL-12 receptor, were elevated over 18 months of treatment, as were levels of soluble vascular cell adhesion molecule-1. The activity of matrix metalloproteinase-9 was decreased by treatment. Thus, clinical and MRI outcomes are supported by systemic immunological changes and call for further investigation of minocycline in MS. Multiple Sclerosis 2007; 13: 517-526. http://msj.sagepub.com

A work-efficient GPU algorithm for level set segmentation

We present a novel GPU level set segmentation algorithm that is both work-efficient and step-efficient. Our algorithm: (1) has linear work-complexity and logarithmic step-complexity, both of which depend only on the size of the active computational domain and do not depend on the size of the level set field; (2) limits the active computational domain to the minimal set of changing elements by examining both the temporal and spatial derivatives of the level set field; (3) tracks the active computational domain at the granularity of individual level set field elements instead of tiles without performance penalty; and (4) employs a novel parallel method for removing duplicate elements from unsorted data streams in a constant number of steps. We apply our algorithm to 3D medical images and we demonstrate that in typical clinical scenarios, our algorithm reduces the total number of processed level set field elements by 16× and is 14× faster than previous GPU algorithms with no reduction in segmentation accuracy.

Deep grey matter "black T2" on 3 tesla magnetic resonance imaging correlates with disability in multiple sclerosis

T2 hypointensity (black T2, BT2) in the deep grey matter of multiple sclerosis (MS) patients correlate weakly with disability at 1.5 T. BT2 is likely to be caused by abnormal iron deposition. We compared the correlation between disability and deep grey matter BT2 measured on 3 T MRI and on 1.5 T MRI in 17 MS patients. We observed a significant correlation between expanded disability status scale and signal intensity on 3 T MRI in the globus pallidus and the caudate nucleus (r = —0.5, P < 0.05). BT2 at 3 T may be a useful MRI measure associated with disability in MS and warrants further study. Multiple Sclerosis 2007; 13: 880—883. http://msj.sagepub.com

Distributed vector processing of the S-transform for medical applications

The recently developed Stockwell transform (ST) combines features of the Fourier and Wavelet transforms; it reveals frequency variation over both space and time. It is a potentially powerful tool that can be applied to medical image processing including tissue texture analysis and noise filtering. However, calculation of the ST is computationally intensive, making conventional implementations too slow for medical applications. This problem was addressed with a Fast Fourier transform implementation for Motorolas AltiVec vector processor and a distributed processing system with the goal of creating a flexible system utilizing existing hardware and standards.

T2 MRI texture analysis is a sensitive measure of tissue injury and recovery resulting from acute inflammatory lesions in multiple sclerosis.

T2 hyperintensity is pathologically non-specific in multiple sclerosis (MS) yet lesion analysis remains an important disease outcome. Texture analysis based on the polar Stockwell Transform (PST) was performed on twelve acute T2 lesions before, during, and after the development of gadolinium-enhancement. When regular myelin structure is disrupted coarse texture increases because tissue becomes disorganized. Coarse texture was quantified as the sum of low frequency energy (sumLFE). Matching regions of contralateral and general normal appearing white matter (NAWM) and chronic T2 lesions were analyzed in parallel as controls. Coarse texture increased in acute lesions during enhancement (p<0.05) then variably recovered. It remained stable in NAWM and tended to increase in chronic T2 lesions. Seven of twelve acute lesions persisted visually at 8 months and the sumLFE was higher in these visually persistent lesions (p<0.05) than in resolved lesions. The sumLFE at month 8 correlated with that in pre-lesional NAWM and in acute lesions (p<0.05) and was independent of lesion volume, signal intensity (SI), and location. This study suggests that PST texture analysis extracts more information about tissue integrity than conventional MRI analysis that relies on lesion size and SI. Texture analysis also appears to identify abnormalities in pre-lesional NAWM, to measure tissue injury in acute lesions, predict poor recovery, and detect mild ongoing tissue injury in chronic T2 lesions. PST texture analysis using conventional MRI may therefore provide valuable new insights into lesion pathology by measuring tissue integrity. This small longitudinal study supports further validation of the PST technique.

3 T deep gray matter T2 hypointensity correlates with disability over time in stable relapsing–remitting multiple sclerosis: A 3-year pilot study

Abnormally decreased deep gray matter (GM) signal intensity on T2-weighted MRI (T2 hypointensity) is associated with brain atrophy and disability progression in patients with multiple sclerosis (MS) and is believed to represent excessive iron deposition. We investigated the time course of deep GM T2 hypointensity and its relationship with disability at 3T in 8 stable relapsing-remitting (RR) MS patients treated with minocycline over 3years. MRI and disability measurements were compared at baseline, 6, 12, 24, and 36months. Grand mean deep GM T2 hypointensity was negatively correlated with EDSS over time (r=-0.94, P=0.02). This correlation was strongest in the head of caudate (r=-0.95, P=0.01) and putamen (r=-0.89, P=0.04). Additionally, baseline grand mean deep GM T2 hypointensity appears to predict third year EDSS (r=-0.72, P=0.04). These results suggest that iron associated deep GM injury correlates with patient disability in stable RRMS. Measurements of deep GM T2 hypointensity at high field MRI may prove to be useful in monitoring individuals with MS. Further studies are required to confirm these results in a large sample and to determine if T2 hypointensity changes in clinically active MS patients.

Distributed vector Processing of a new local MultiScale Fourier transform for medical imaging applications

The recently developed S-transform (ST) combines features of the Fourier and Wavelet transforms; it reveals frequency variation over both space and time. It is a potentially powerful tool that can be applied to medical image processing including texture analysis and noise filtering. However, calculation of the ST is computationally intensive, making conventional implementations too slow for many medical applications. This problem was addressed by combining parallel and vector computations to provide a 25-fold reduction in computation time. This approach could help accelerate many medical image processing algorithms.

Sketch-based volumetric seeded region growing

Interactive volume segmentation is an essential and important step in medical image processing. Conventional interactive methods typically demand significant amounts of time and do not lend to a natural interaction scheme with the 3D volume. In this paper we present a sketch-based interface for seeded region growing volume segmentation. In our approach, the user freely sketches regions of interest (ROI) directly over the 3D volume. Parts of the volume outside the ROIs are then automatically cut out in real-time. The user repeats this process as many times as necessary until he/she decides to specify the seed point 3D location directly at the ROI. To prevent unexpected segmentations, the region growing is restricted to the specified ROI. Our sketch-based system utilizes GPU programming to achieve real-time processing for both rendering and volumetric cutting independent from the size and shape of the sketched strokes.

Real-time super resolution contextual close-up of clinical volumetric data

We present an illustrative visualization system for real-time and high quality rendering of clinical volumetric medical data. Our technique is inspired by a medical illustration technique for depicting contextual close-up views of selected regions of interest where internal anatomical features are rendered in high detail. Our method integrates four important components: decimation of original volume for interactivity, B-spline subdivision for super-resolution rendering, fast gradient quantization technique for feature extraction and GPU fragment shaders for gradient dependent rendering and transfer functions. Examples with clinical CT and MRI data demonstrate the capabilities of our system.

Corpus callosum volume and interhemispheric transfer in multiple sclerosis

BACKGROUND The corpus callosum (CC) is frequently compromised in patients with multiple sclerosis (MS). Structural and functional measurements of the CC may be useful to monitor the progression of the disease. The aim of this pilot study was to determine if bimanual tactile temporal thresholds correlates with CC volume. A tactile temporal threshold is the longest temporal interval that separates the onsets of two tactile stimuli when they are judged by the observer as simultaneous. Judgments to bimanual stimulations require interhemispheric transfer via the CC. METHODS Thresholds were examined in MS patients and matched controls. Magnetic resonance (MR) images were acquired on a 3T MR system within 48 hours of clinical assessment and measurement of thresholds. RESULTS Corpus callosum volume was assessed by using a semiautomatic livewire algorithm. The CC volume was smaller (by 21% on average, p < 0.01) and thresholds were higher (by 49% on average, p < 0.03) in MS patients when compared to controls. A significant correlation (r = -0.66, p = 0.01) between CC volume and thresholds emerged for the MS patients. CONCLUSION Measuring treatment benefits of neuroprotective and repair therapies is a well recognized challenge in MS research. The overall findings of this study suggest that these measurements, which involve the transfer of information interhemispherically via the CC, may be promising outcome measures that warrant further scientific exploration to develop a model to measure recovery.