Robert I. Grossman

Multiple sclerosis lesion quantification using fuzzy-connectedness principles

Multiple sclerosis (MS) is a disease of the white matter. Magnetic resonance imaging (MRI) is proven to be a sensitive method of monitoring the progression of this disease and of its changes due to treatment protocols. Quantification of the severity of the disease through estimation of MS lesion volume via MR imaging is vital for understanding and monitoring the disease and its treatment. This paper presents a novel methodology and a system that can be routinely used for segmenting and estimating the volume of MS lesions via dual-echo fast spin-echo MR imagery. A recently developed concept of fuzzy objects forms the basis of this methodology. An operator indicates a few points in the images by pointing to the white matter, the grey matter, and the cerebrospinal fluid (CSF). Each of these objects is then detected as a fuzzy connected set. The holes in the union of these objects correspond to potential lesion sites which are utilized to detect each potential lesion as a three-dimensional (3-D) fuzzy connected object. These objects are presented to the operator who indicates acceptance/rejection through the click of a mouse button. The number and volume of accepted lesions is then computed and output. Based on several evaluation studies, the authors conclude that the methodology is highly reliable and consistent, with a coefficient of variation (due to subjective operator actions) of 0.9% (based on 20 patient studies, three operators, and two trials) for volume and a mean false-negative volume fraction of 1.3%, with a 95% confidence interval of 0%-2.8% (based on ten patient studies).

The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis

Article abstract MRI is very sensitive in showing MS lesions throughout the CNS. Using MRI for diagnostic purposes, however useful, is a complex issue because of limited specificity of findings and a variety of options as to when, how, and which patients to examine. Comparability of data and a common view regarding the impact of MRI are needed. Following a review of the typical appearance and pattern of MS lesions including differential diagnostic considerations, we suggest economic MRI examination protocols for the brain and spine. Recommendations for referral to MRI consider the need to avoid misdiagnosis and the probability of detecting findings of diagnostic relevance. We also suggest MRI classes of evidence for MS to determine the diagnostic weight of findings and their incorporation into the clinical evaluation. These proposals should help to optimize and standardize the use of MRI in the diagnosis of MS.

NMR relaxation times of blood: dependence on field strength, oxidation state, and cell integrity.

The variation with field strength or interecho interval of the T1 and T2 relaxation times of oxyhemoglobin (HbO2), deoxyhemoglobin (Hb), and methemoglobin (MHb) in either intact or lysed red blood cells was studied with a variable field (0.19–1.4 T) nuclear magnetic resonance spectroscopy unit. The T2 relaxation time of intracellular HbO2 decreased slightly with increasing field strength and interecho interval. The T2 relaxation times of intracellular Hb and MHb decreased markedly with increasing field strength and interecho interval. This T2 proton relaxation enhancement increased as the square of the applied field strength and was 1.6 times stronger for intracellular MHb than for intracellular Hb. The T2 relaxation enhancement is secondary to the loss of transverse phase coherence of water protons that diffuse across cellular magnetic field gradients. These field gradients occur when an external field is applied to a region with gradients of magnetic susceptibility. The heterogeneity of magnetic susceptibility is caused by the heterogeneous distribution (only intracellular) of the paramagnetic molecules (Hb or MHb). The T2 relaxation times of red cell lysates (homogeneous magnetic susceptibility) were independent of field strength or interecho interval. There was a decrease in the T1 relaxation times when the red cells were lysed. This may be due to an increase in the slow motional components of water molecules, because of the decrease in the average distance between water and hemoglobin molecules in the lysate. The Tl relaxation times of all the MHb samples were shortened because of proton-electron dipolar-dipolar relaxation enhancement. All the Tl relaxation times increased with increasing field strength.

Total brain N-acetylaspartate A new measure of disease load in MS

Objective: To quantitate the extent of neuronal cell loss in MS via the whole brain’s N-acetylaspartate (NAA) concentration (WBNAA). Methods: Because NAA is assumed to be present only in neuronal cell bodies and their axons, we measured WBNAA as a marker for viable neurons in 12 patients (9 women and 3 men, 26 to 53 years of age) suffering from relapsing-remitting (RR) MS for at least 5 years and compared them with 13 age- and sex-matched normal controls. Total brain NAA was determined with proton MR spectroscopy, and WBNAA was obtained by dividing it by the total brain volume, calculated from high resolution MRI. Results: The WBNAA of the RR MS patients was lower than their matched controls (p < 0.005). This difference was greater among older than younger subjects. The linear prediction equations of WBNAA with age indicate a faster, ×10, decline in the patients, ∼0.8% per year of age (p = 0.022). Conclusion: The age-dependent decrease of whole brain N-acetylaspartate (WBNAA) in the patients suggests that progressive neuronal cell loss is a cardinal feature of this disease. WBNAA offers a quick, highly reproducible measure of disease progression and may be an important marker of treatment efficacy in MS as well as other neurodegenerative diseases.

Correlation of volumetric magnetization transfer imaging with clinical data in MS

We examined the relations between quantitative volumetric estimates of cerebral lesion load based on magnetization transfer imaging (MTI), clinical data, and measures of neuropsychological function in 44 patients with clinically diagnosed MS. In this population we assessed the correlation between several volumetric MTI measures, measures of neurologic function (Kurtzke Expanded Disability Status Scale and Ambulation Index), and disease duration using Spearmans correlation coefficient. Patients were classified on the basis of neuropsychological test performance as severely impaired, moderately impaired, and normal. We assessed differences between these groups with respect to MTI results using the Kruskal-Wallis test. MTI measures corrected for brain volume were found to correlate with disease duration (p < 0.01) and showed suggestive correlations with measures of neurologic impairment (p < 0.05). Individual neuropsychological tests correlated with MTI measures corrected and not corrected for brain volume (p < 0.001). An MTI measure not corrected for brain volume differed (p < 0.05) between severely impaired, moderately impaired, and normal patients. These preliminary results suggest that volumetric MTI analysis provides new measures that reflect more accurately the global lesion load in the brain of MS patients, and they may serve as a method to study the natural course of the disease and as an outcome measure to evaluate the effect of drugs.

High Field Mr Imaging of Cerebral Venous Thrombosis

High field magnetic resonance (MR) imaging enables us to demonstrate the evolution of cerebral venous thrombosis. Initially, absence of a flow void and collateral venous channels are seen on T1 weighted images (WI). On T2WI thrombus appears hypointense. Hyperintensity is noted in an intermediate stage of thrombosis first on T1WI and later on T2WI. In the late stages recanalization of the vessel occurs with reappearance of the flow void. These findings are specific for venous thrombosis. High field MR may be the imaging modality of choice in the diagnosis of venous thrombosis.

Thalamus and Cognitive Impairment in Mild Traumatic Brain Injury: A Diffusional Kurtosis Imaging Study

Conventional imaging is unable to detect damage that accounts for permanent cognitive impairment in patients with mild traumatic brain injury (mTBI). While diffusion tensor imaging (DTI) can help to detect diffuse axonal injury (DAI), it is a limited indicator of tissue complexity. It has also been suggested that the thalamus may play an important role in the development of clinical sequelae in mTBI. The purpose of this study was to determine if diffusional kurtosis imaging (DKI), a novel quantitative magnetic resonance imaging (MRI) technique, can provide early detection of damage in the thalamus and white matter (WM) of mTBI patients, and can help ascertain if thalamic injury is associated with cognitive impairment. Twenty-two mTBI patients and 14 controls underwent MRI and neuropsychological testing. Mean kurtosis (MK), fractional anisotropy (FA), and mean diffusivity (MD) were measured in the thalamus and several WM regions classically identified with DAI. Compared to controls, patients examined within 1 year after injury exhibited variously altered DTI- and DKI-derived measures in the thalamus and the internal capsule, while in addition to these regions, patients examined more than 1 year after injury also showed similar differences in the splenium of the corpus callosum and the centrum semiovale. Cognitive impairment was correlated with MK in the thalamus and the internal capsule. These findings suggest that combined use of DTI and DKI provides a more sensitive tool for identifying brain injury. In addition, MK in the thalamus might be useful for early prediction of permanent brain damage and cognitive outcome.

Magnetic resonance imaging in Parkinson's disease and parkinsonian syndromes

High field strength magnetic resonance imaging (MRI) provides a noninvasive means of evaluating patients with parkinsonism. Using strict clinical criteria, we began a prospective study of patients with Parkinsons disease (PD) and parkinsonian syndromes (PS) including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and atypical parkinsonism (ATYP). We detected moderate to severe putaminal hypointensity more frequently in PS than in PD and controls, although putaminal hypointensity did not distinguish between MSA, PSP, or ATYP. Signal intensity in the lateral substantia nigra did not differ significantly among patients with PD, PS, or controls and was therefore not a useful MRI marker. Pars compacta width was significantly narrower in both PD and PS. Subcortical and periventricular hyperintense foci were more abundant in PD and PS than controls. Atrophy of the brainstem occurred only in patients with PS.

MRI techniques to monitor MS evolution: The present and the future

Abstract—Conventional MRI (cMRI) is limited in its ability to provide specific information about pathology in MS. Measures commonly derived from cMRI include T2 lesions, T1-enhanced lesions, atrophy, and possibly T1-hypointense lesions, which have been extensively investigated in many clinical trials. Better MRI measures are needed to advance our understanding of MS and design ideal clinical trials. This article reviews the strengths and weaknesses of the major MRI-based methods used to monitor MS evolution and submits that 1) metrics derived from magnetization transfer MRI, diffusion-weighted MRI, and proton MRS should be implemented to achieve reliable specific in vivo quantification of MS pathology; 2) targeted multiparametric MRI protocols rather than generic application of cMRI should be used in all possible clinical circumstances and trials; and 3) reproducible quantitative MR measures should ideally be used for the assessment of patients but are essential for clinical trials.

Aspergillosis of the nervous system

Cerebral aspergillosis currently occurs most frequently with disseminated aspergillosis in immunocompromised hosts. Twelve patients with cerebral aspergillosis in this setting were seen over 10 years. Underlying illnesses were renal transplantation in six cases and one case each of subacute hepatic necrosis, head trauma, glioblastoma, microglioma, and esthesioneuroblastoma. All patients were receiving high dose steroid therapy except one who had ectopic ACTH syndrome. Eleven patients were receiving broad spectrum antibiotics. All patients were febrile and developed progressive pulmonary infiltrates preceding or coincident with neurologic symptoms. Sudden onset of neurologic deficits or seizures occurred in nine of 11 clinically analyzable cases. Brainstem or cerebellar signs and symptoms were a presenting feature in three cases and were eventually seen in five cases. Cranial computerized tomography in four cases showed low absorption areas with minimal enhancement and little mass effect. Neurologic deterioration was rapid with nine of 11 patients dying within 6 days of onset. Neuoropathologic examination showed multiple abscess formation in 11 cases and prominent blood vessel invasion in all cases. The sudden onset of stroke-like deficits and brainstem findings in a febrile immunocompromised host with pulmonary infiltrates suggests the diagnosis of cerebral aspergillosis. Two cases of Aspergillus meningitis were also seen, one postoperatively.