1H Magnetic Resonance Spectroscopic Imaging (MRSI) is the only non-invasive technique capable of measuring chemicals within the body and can be performed on many conventional Magnetic Resonance Imaging (MRI) systems. MRSI exploits the principle that every chemically distinct nucleus in a compound resonates at a slightly different frequency, allowing the detection of a wide variety of proton signals on a given proton. In addition, the NMR signals from many compounds can be detected simultaneously in one MRS experiment and MRSI with phase encoding could obtain MRS signals from multiple regions simultaneously.
1H MRSI detects N-acetyl aspartate (NAA), lactate, choline (Cho), creatine (Cr) phosphocreatine, and amino acids including glutamate, glutamine, aspartate, and taurine. NAA appears to be a neuronal marker not being found in mature glial cells.1 Lactate provides information concerning bioenergetics. Choline provides information concerning lipid metabolism. MRSI single volume localization techniques, using several pulses and gradients, offer the advantages of sharp spatial resolution and high sensitivity. Spectroscopic imaging techniques (using phase encoding) have the important advantage that multiple regions are sampled simultaneously, at a cost of a less well-defined point spread function. For clinical investigation, it is essential that MRSI is quantitated to provide reducible clinical data from specific tissue regions.2
1. Alzheimer’s Disease
Alzheimer’s Disease (AD), the most common cause of dementia, is difficult to diagnose (with any certainty) early in its course.3-7 Even when the patients become demented, the antemortem diagnosis of Alzheimer’s Disease by most family physicians is imperfect and is variable depending on the examiners. There is a need for improved objective and quantifiable tests for monitoring its progression and response to treatment. MRSI together with MRI has substantial promise as an objective non-invasive technique for screening, diagnosis and therapy monitoring. MRI is frequently used as a routine diagnostic technique and MRSI detects NAA (a neuron-specific marker) and other metabolites which are altered (possibly in a specific pattern) in Alzheimer’s Disease. It is expected that MRSI will detect neuronal loss, and like 18Fluorodeoxyglucose-Positron Emission Tomography (18FDG-PET) will also detect metabolic changes in the hippocampus, temporal, frontal, and parietal cortices. It is expected that the anatomical pattern of these changes will correlate with specific cognitive impairments. Therefore, the significance of the proposed work is that it will lead to:
(1) A greater understanding of the pathophysiology of Alzheimer’s Disease, which may contribute to the development of improved therapy.
(2) Improved clinically useful measures which provide sensitive and specific antemortem diagnosis for, and early screening of, Alzheimer’s Disease.
(3) Objective, quantifiable measures which can be used to stage patients for clinical trials, monitor the progression of dementia, and quantitate the effects of therapy for Alzheimer’s Disease.
The effects of AD can be seen on functional and structural imaging of the brain. With MRI patients with AD often show global cerebral atrophy with sulcal and ventricular enlargement. The ratio of NAA determined with MRSI suggests that this technique may provide useful adjunctive information in diagnosis of AD when used in combination with standard clinical and neuropsychological evaluations. Moreover, MRSI may provide new insights into the pathogenesis of the disorder. Brain function, measured as glucose metabolism with PET, is selectively affected in frontal, parietal, and temporal association cortex with relative sparing of the primary cortex, basal ganglia and thalamus.
Epilepsy is an episodic disorder of the nervous system, arising from the excessively synchronous and sustained discharge of a group of neurons. MRI provides the best anatomic detail of any imaging modality. It is clearly superior to all other imaging modalities for the detection of mass lesions (neoplasms, vascular malformations) and currently is the principal imaging technique for evaluating patients with partial epilepsy.36,37 The anatomic detail provided by MRI has made the detection of most mass lesions straightforward. The importance of this capability for epilepsy surgery candidates cannot be overstated. In patients with mass lesions detected by MRI, epilepsy surgery usually results in a good outcome.38 The difference in outcome between “lesional” and “non-lesional” patients is particularly noticeable for patients with extra-temporal foci; a recent multicenter survey showed that 67% of extra-temporal “lesionectomy” patients became seizure-free while only 44% of “non-lesional” patients became seizure-free.39 In addition, MRI allows the nature of the lesion to be deduced preoperatively, enabling the surgeon to make directed plans.
MRI is the cornerstone of providing the anatomical alterations in epilepsy patients. MRSI allows for evaluation of the resonance of NAA, Cr and Cho. MRSI sensitively detects diminished NAA within the epileptogenic region in epilepsy patients, suggesting that this technique may be useful as a tool for localizing the epileptogenic region in all patients with partial epilepsy. The greatest diagnostic sensitivity for temporal EEG abnormalities can be provided by PET measurement of metabolism using fluorodeoxyglucose.