MRI techniques: bilateral findings and "normal findings"

Magnetic resonance imaging (MRI) techniques allow for significantly better imaging of the temporal lobe compared to computed tomography (CT) or other non-invasive modalities. For detection of foreign tissue lesions, MRI surpasses CT. For the highest non-invasive yield for detection of mesial temporal sclerosis, optimal sequences that should be employed are a heavily T1-weighted volumetric acquisition (to enable both volumetric calculation of hippocampal volume, and, if needed, intracranial volume), T2-weighted coronal sequences, with or without T2-mapping, fluid-attenuated inversion recovery (FLAIR) and, to exclude subtle susceptibility effects from hematoma or cavernoma, gradient echo scans. Magnetic resonance spectroscopy (MRS) may show a decrease in N-acetyl aspartate (NAA) concentration, or NAA: Choline + creatine ratio. Functional MRI is a new and exciting tool that offers the promise of accurately localizing hemispheric functions; its role in the preoperative evaluation of temporal lobe seizures remains uncertain at present.     

MRS Findings in Cerebral Coenurosis due to Taenia Multiceps

Cerebral coenurosis due to Taenia multiceps is a rare infection with no case reports from India. A 55‐year‐old male patient had presented with progressive symptoms of hemiparesis of 1‐year duration. Magnetic resonance imaging (MRI) with magnetic resonance spectroscopy (MRS) of the lesion was performed that showed a septated cystic lesion in left parieto‐occipital lobe. Multivoxel MRS through the lesion was performed using repetition time of 1500 ms and time to echo of 144 ms at 3T MRI. MRS showed mildly elevated choline (Cho), depressed creatine (Cr), and N‐acetyl aspartate (NAA), a large peak of lactate, pyruvate, and acetate peaks. To best of our knowledge, there has been no reported case of in vivo proton MRS finding ever reported. We present MRS findings in this operatively proven case of T. multiceps cyst of the brain.     

Linking structural, metabolic and functional changes in multiple sclerosis

In patients with multiple sclerosis (MS), conventional magnetic resonance imaging (MRI) has markedly improved our ability to detect the macroscopic abnormalities of the brain and spinal cord. New quantitative magnetic resonance (MR) approaches with increased sensitivity to subtle normal-appearing white matter (NAWM) and grey matter changes and increased specificity to the heterogeneous pathological substrates of MS may give information complementary to conventional MRI. Magnetization transfer imaging (MTI) and diffusion-weighted imaging (DWI) have the potential to provide important information on the structural changes occurring within and outside T2-visible lesions. Magnetic resonance spectroscopy (MRS) adds information on the biochemical nature of such changes. Functional MRI might quantify the efficiency of brain plasticity in response to MS injury and improve our understanding of the link between structural damage and clinical manifestations. The present review summarizes how the application of these MR techniques to the study of MS is dramatically changing our understanding of how MS causes irreversible neurological deficits.     

Understanding pathogenesis and treatment of HIV dementia: a role for magnetic resonance?

HIV dementia (HIVD) is among the most common and most feared neurological complications of AIDS. In vitro studies have identified a constellation of potentially neurotoxic inflammatory and non-inflammatory pathways, one or more of which could underlie HIVD. Magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) studies can distinguish between inflammatory and non-inflammatory pathways in vivo and suggest that either or both might be active in different patients or at different times in the same patient. This could perhaps explain the variability in HIVD development, progression and response to therapy. These findings also suggest that MRI and MRS can identify patients at risk for HIVD and predict response to therapy.     

Valproate-induced encephalopathy: assessment with MR imaging and 1H MR spectroscopy

The anticonvulsant agent valproate (VPA) may cause hyperammonemic encephalopathy. Magnetic resonance imaging (MRI) and proton MR spectroscopic (MRS) findings in a patient with VPA-induced hyperammonemic encephalopathy are described. MRI showed a metabolic-toxic lesion pattern with bilateral T2-hyperintense lesions in the cerebellar white matter and in the globus pallidus. MR spectroscopic findings were indistinguishable from hepatic encephalopathy with severe depletion of myoinositol and choline and with glutamine excess. N-Acetylaspartate levels were moderately decreased. Quantitative MRS gave detailed insight into alterations of brain metabolism in VPA-induced encephalopathy.     

Clinically benign multiple sclerosis despite large T2 lesion load: can we explain this paradox?

Magnetic resonance imaging (MRI) techniques such as magnetization transfer imaging and magnetic resonance spectroscopy (MRS) may reveal otherwise undetectable tissue damage in multiple sclerosis (MS) and can serve to explain more severe disability than expected from conventional MRI. That an inverse situation may exist where non-conventional quantitative MRI and MRS metrics would indicate less abnormality than expected from T2 lesion load to explain preserved clinical functioning was hypothesized. Quantitative MRI and MRS were obtained in 13 consecutive patients with clinically benign MS (BMS; mean age 44 +/- 9 years) despite large T 2 lesion load and in 15 patients with secondary progressive MS (SPMS; mean age 47 +/- 6 years) matched for disease duration. The magnetization transfer ratio (MTR), magnetization transfer rate (kfor), brain parenchymal fraction (BPF) and brain metabolite concentrations from proton MRS were determined. BMS patients were significantly less disabled than their SPMS counterparts (mean expanded disability status score: 2.1 +/- 1.1 versus 6.2 +/- 1.1; P < 0.001) and had an even somewhat higher mean T2 lesion load (41.2 +/- 27.1 versus 27.9 +/- 24.8 cm3; P = 0.19). Normal appearing brain tissue histogram metrics for MTR and kfor, mean MTR and kfor of MS lesions and mean BPF were similar in BMS and SPMS patients. Levels of N-acetyl-aspartate, choline and myoinositol were comparable between groups. This study thus failed to explain the preservation of function in our BMS patients with large T2 lesion load by a higher morphologic or metabolic integrity of the brain parenchyma. Functional compensation must come from other mechanisms such as brain plasticity.     

In vivo visualization of focal demyelination in peripheral nerves by gadofluorine M-enhanced magnetic resonance imaging

Magnetic resonance imaging (MRI) allows assessment of axonal nerve lesions, but detection of focal demyelination is still difficult. We have recently shown that the novel micellar magnetic resonance (MR) contrast agent gadofluorine M (Gf) accumulates in nerve fibers undergoing Wallerian degeneration. In the present study, we report on the in vivo visualization of focal demyelination induced by lysolecithin. Upon appropriate intraneural injection, lysolecithin focally dissolves myelin sheaths with sparing of axons. Conventional unenhanced and gadolinium-DTPA enhanced T1-w MRI did not show signal alterations or contrast enhancement. In contrast, application of Gf led to bright contrast enhancement on T1-w images at the site of focal demyelination, but spared distal nerve segments not affected by demyelination. Gf enhancement persisted until remyelination had occurred. Our study shows that areas of focal nerve demyelination can be detected in vivo by Gf-enhanced MRI. This finding opens up a broad spectrum of applications in experimental neurology, and, depending on further clinical development of Gf, may aid in the diagnostic work up of patients with patchy, multifocal demyelinative disorders in the future.     

High resolution magnetic resonance imaging of the brain in the dy/dy mouse with merosin-deficient congenital muscular dystrophy

Magnetic resonance imaging (MRI) abnormalities in the cerebral white matter are a consistent feature of merosin-deficient human congenital muscular dystrophy, a disease caused by a primary defect in the expression of the laminin alpha2 chain of merosin. To investigate the relationship between imaging changes and merosin deficiency we undertook a MRI study in the dy/dy mouse, an animal model for this form of human congenital muscular dystrophy. High resolution in vivo imaging was performed on anaesthetized animals (two homozygous dy/dy mutants and two heterozygous dy/DY controls, aged 2.5 months) in a dedicated 11.7T magnetic resonance imaging scanner. T(1) and T(2) weighted images were normal in all mice and white matter changes were not seen at a stage of maturity when MRI changes are already very striking in human patients. Cerebral MRI abnormalities do not appear to be a feature of dy/dy mice, despite the virtual absence of merosin expression in the dy/dy mouse brain. Possible causes for this absence of MRI changes, and implications for the pathogenesis of the MRI changes in humans are reviewed.     

Magnetic resonance spectroscopy in psychiatry: potential, pitfalls, and promise

Magnetic resonance spectroscopy (MRS) is a novel noninvasive approach to measuring important metabolites in living tissue. Its application to psychiatry is just beginning. In vivo MRS with 31P provides important information on brain phospholipid metabolism and energy production. In vivo 13C and 1H MRS can reveal information about carbohydrate, protein, and amino acid metabolism. In vivo 7Li and 19F MRS can be used to study the pharmacology of lithium and fluorinated psychopharmacological agents. MRS with 23Na can yield information about electrolyte balance. The limitations of in vivo MRS include poor sensitivity, poor resolution, and the fact that only highly mobile atomic nuclei can be detected. Future clinical application of MRS will benefit from improvements in the technology of localization, use of spectroscopy contrast agents, stronger magnets, and the merging of MRS and imaging technology.     

Magnetic resonance spectroscopyin vivo: applications in neurological disorders

Magnetic resonance (MR) spectroscopy (MRS) is performed using the same magnets and computers as conventional MR imaging (MRI), However, unlike conventional MRI, which provides structural information, MRS provides chemical information that represents pathologically specific measures useful for diagnosis and monitoring of patients affected by neurological disorders. This review will focus on selected clinical applications of MRS that have been demonstrated to have clinical use. These include phosphorus MRS of muscle to diagnose metabolic muscle disease, and proton MRS of brain to lateralize temporal lobe epilepsy, to classify brain tumors, and to evaluate the natural history and pathology of multiple sclerosis.     

Characterization of ataxias with magnetic resonance imaging and spectroscopy

A wide variety of autosomal transmitted ataxias exist and their ultimate characterization requires genetic testing. Common clinical characteristics among different ataxia types complicate the choice of the appropriate genetic test. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) generally show cerebellar or cerebral atrophy and perturbed metabolite levels which differ between ataxias. In order to help the clinician accurately identify the ataxia type, reported MRI and MRS data in different brain regions are summarized for more than 60 different types of autosomal inherited and sporadic ataxias.     

Magnetic resonance imaging of labeled T-cells in a mouse model of multiple sclerosis

Multiple sclerosis (MS) is a T cell-mediated autoimmune disease with early lesions characterized by mononuclear cellular infiltrate, edema, demyelination, and axonal loss that contribute to the clinical course of the disease. Experimental autoimmune encephalomyelitis (EAE) in the mouse is a valuable model with a similar disease course to relapsing-remitting MS. The ability to detect the migration of encephalitogenic T cells into the central nervous system in EAE and MS would provide key information on these cells role in the development of lesions observed on magnetic resonance imaging (MRI). T cells were labeled for detection by magnetic resonance imaging using Food and Drug Administration-approved, superparamagnetic iron oxide nanoparticles (Ferumoxides) complexed to poly-L-Lysine (FE-PLL). EAE was induced by adoptive transfer of either labeled or unlabeled T cells. After disease onset, FE-PLL-labeled T cells were detected in the mouse spinal cord using in vivo and ex vivo cellular MRI. Excellent correlation was seen between MRI-visible lesions in the spinal cord and histopathology. The results demonstrate that T cells labeled with FE-PLL can induce EAE disease and can be detected in vivo in the mouse model. The magnetic labeling of cells opens the possibility of monitoring specific cellular phenotypes or pharmacologically or genetically engineered cells by MRI.     

Magnetic resonance spectroscopy.

Magnetic resonance spectroscopy (MRS) complements magnetic resonance imaging (MRI) as a non-invasive means for the characterization of tissue. While MRI uses the signal from hydrogen protons to form anatomic images, proton MRS uses this information to determine the concentration of brain metabolites such as N-acetyl aspartate (NAA), choline (Cho), creatine (Cr) and lactate in the tissue examined. The most widely used clinical application of MRS has been in the evaluation of central nervous system disorders.MRS has its limitations and is not always specific but, with good technique and in combination with clinical information and conventional MRI, can be very helpful in diagnosing certain entities. For example, a specific pattern of metabolites can be seen in disorders such as Canavan's disease, creatine deficiency, and untreated bacterial brain abscess. MRS may also be helpful in the differentiation of high grade from low grade brain tumors, and perhaps in separating recurrent brain neoplasm from radiation injury.     

Magnetic resonance imaging and magnetic resonance spectroscopy for detection of early Alzheimer's disease

Alzheimer's disease is the most common form of neurodegenerative disorder and early detection is of great importance if new therapies are to be effectively administered. We have investigated whether the discrimination between early Alzheimer's disease (AD) and elderly healthy control subjects can be improved by adding magnetic resonance spectroscopy (MRS) measures to magnetic resonance imaging (MRI) measures. In this study 30 AD patients and 36 control subjects were included. High resolution T1-weighted axial magnetic resonance images were obtained from each subject. Automated regional volume segmentation and cortical thickness measures were determined for the images. 1H MRS was acquired from the hippocampus and LCModel was used for metabolic quantification. Altogether, this yielded 58 different volumetric, cortical thickness and metabolite ratio variables which were used for multivariate analysis to distinguish between subjects with AD and Healthy controls. Combining MRI and MRS measures resulted in a sensitivity of 97% and a specificity of 94% compared to using MRI or MRS measures alone (sensitivity: 87%, 76%, specificity: 86%, 83% respectively). Adding the MRS measures to the MRI measures more than doubled the positive likelihood ratio from 6 to 17. Adding MRS measures to a multivariate analysis of MRI measures resulted in significantly better classification than using MRI measures alone. The method shows strong potential for discriminating between Alzheimer's disease and controls.     

Proton magnetic resonance spectrometry for the non-invasive exploration of human brain metabolism: current and future clinical applications

Magnetic resonance spectrometry (MRS) is now a routine investigation method in neurology. In some situations, its diagnostic sensitivity is better than MRI. In this review, we propose a critical analysis of the large body of literature on brain MRS concerning a wide range of pathologies and many different protocols. The diagnostic value of MRS is not fully determined in all neurological diseases, but the specific properties of MRS (detection of neuron-specific and glial-specific metabolites, quantitative data, reversibility of metabolic lesions) make it a high-performance tool for quantifying neuron, glial and membrane abnormalities. After reviewing the methodological advances in MRS and discussing restrictions on interpretation of spectral data, we describe variations in metabolic patterns detected by MRS in different groups of diseases. The currently reasonable indications for MRS exploration are presented as well as new avenues for research. Based on MRS data, we propose a metabolic definition of encephalopathy which could be useful in better understanding the role of MRS in modern neurology.     

Comparison of Premortem Magnetic Resonance Imaging and Postmortem Autopsy Findings of a Cortical Microinfarct

An 85-year-old woman diagnosed with amyotrophic lateral sclerosis died of pneumonia and was autopsied. Magnetic resonance imaging (MRI) performed 16 days before death revealed an intracortical high-intensity lesion in her right temporal cortex on three-dimensional (3D)-double inversion recovery (DIR) and 3D-fluid-attenuated inversion recovery (FLAIR) images. Histopathological examination indicated a cortical microinfarct (CMI) juxtaposed to cerebral amyloid angiopathy. Recently, in vivo detection of CMIs using 3D-DIR and 3D-FLAIR on 3-tesla MRI has been reported, and postmortem MRI study confirmed the presence of CMIs. This is the first case study to compare CMI findings detected upon premortem MRI to the CMI itself discovered upon postmortem neuropathological examination.     

Effects of Vigabatrin on the GABAergic System as Determined by [123I]Iomazenil SPECT and GABA MRS

PURPOSE: To evaluate effects of vigabatrin (VGB) by using [123I]iomazenil single-photon emission computed tomography (SPECT) to estimate central gamma-aminobutyric acid (GABA(A))/benzodiazepine receptors (BZRs), and magnetic resonance spectroscopy (MRS) to assess tissue GABA levels. METHODS: Six patients with partial seizures had both SPECT and MRS before and 25-84 days after starting VGB (3 g p.o., q.d.). SPECT was acquired by using the constant-infusion method and, after nonuniform attenuation correction, coregistered with T1-weighted MR Imaging (MRI) A volume of interest (VOI) of 3 x 2 x 2 cc over the occipital cortex, used for MRS acquisition, was positioned on both MRI and coregistered SPECT. Occipital activity was divided by either total plasma activity or plasma [123I]iomazenil concentration to estimate BZR distribution volume (V(T)-p and V'(T), respectively). Wilcoxon's test was used for VOI differences in GABA levels, BZR V(T)-p or V'(T). SPM96 (either no global normalization or proportional scaling) was used to compare BZR V(T)-p changes in the patients with and without VGB with test-retest data in eight healthy age-matched controls. RESULTS: Occipital GABA levels were increased threefold (without VGB, 1.1+/-0.1 micromol/g; with VGB, 2.9+/-0.5 micromol/g; p = 0.027). BZR distribution volumes showed no change, when estimated by either V(T)-p (without VGB, 6.00+/-0.91 ml/g; with VGB, 5.86+/-0.44 ml/g; p = 0.92) or V(T) (without VGB, 41.1+/-11.2 ml/g; with VGB, 41.2+/-9.9 ml/g; p = 0.75). No significant changes were detected by SPM96. CONCLUSIONS: A clinically effective dose of VGB caused a threefold increase in tissue GABA levels but was not associated with a substantial BZR downregulation.     

MR spectroscopy in diagnosis and neurological decision-making

One of the most prolific chemical and anatomical imaging techniques of recent decades, magnetic resonance imaging (MRI), includes the ability to noninvasively assess neurochemical changes with magnetic resonance spectroscopy (MRS). Practical concerns are paramount in applying MRS, such as what the manufacturer provides with a routine MRI scanner, what methods are well tolerated by patients, and what has proved most diagnostically productive over a 25 year span of preliminary exploration of the technology. In this review, the authors explain the technical and neurochemical aspects of MRS and critically discuss its clinical neuroimaging applications.     

Examination of the role of magnetic resonance imaging in multiple sclerosis: A problem-orientated approach

Magnetic Resonance Imaging (MRI) has brought in several benefits to the study of Multiple Sclerosis (MS). It provides accurate measurement of disease activity, facilitates precise diagnosis, and aid in the assessment of newer therapies. The imaging guidelines for MS are broadly divided in to approaches for imaging patients with suspected MS or clinically isolated syndromes (CIS) or for monitoring patients with established MS. In this review, the technical aspects of MR imaging for MS are briefly discussed. The imaging process need to capture the twin aspects of acute MS viz. the autoimmune acute inflammatory process and the neurodegenerative process. Gadolinium enhanced MRI can identify acute inflammatory lesions precisely. The commonly applied MRI marker of disease progression is brain atrophy. Whole brain magnetization Transfer Ratio (MTR) and Magnetic Resonance Spectroscopy (MRS) are two other techniques use to monitor disease progression. A variety of imaging techniques such as Double Inversion Recovery (DIR), Spoiled Gradient Recalled (SPGR) acquisition, and Fluid Attenuated Inversion Recovery (FLAIR) have been utilized to study the cortical changes in MS. MRI is now extensively used in the Phase I, II and III clinical trials of new therapies. As the technical aspects of MRI advance rapidly, and higher field strengths become available, it is hoped that the impact of MRI on our understanding of MS will be even more profound in the next decade.     

Magnetic Resonance Spectroscopy in Animal Models of Epilepsy

Summary:  The noninvasive localization of the epileptogenic zone continues to be a challenge in many patients that present as candidates for possible epilepsy surgery. Magnetic resonance imaging (MRI) techniques provide accurate anatomical definition, but despite their high resolution, these techniques fail to visualize the pathological neocortical and hippocampal changes in a sizable number of patients with focal pathologies. Further, visualized lesions on MRI may not all produce seizures. One of the keys to the understanding of the epileptogenic zone lies in the recognition of the metabolic alterations that occur in the setting of epileptic seizures. Magnetic resonance spectroscopy (MRS) is a valuable tool that can be used to study the metabolic changes seen in both acute and chronic animal models of epilepsy. Such study allows for the identification of epileptic tissue with high sensitivity and specificity. We present here a review of the use of MRS in animal models of epilepsy.