Purpose: To investigate the relationship of myelin content, axonal density, and gliosis with the fraction of macromolecular protons (f B ) and T 2 relaxation of the macromolecular pool (T 2B ) acquired using quantitative magnetization transfer (qMT) MRI in postmortem brains of subjects with multiple sclerosis (MS). Conclusion: f B in MS WM is dependent on myelin content and may be a tool to monitor patients with this condition. Materials and Methods
In this study, diffusion-weighted images of the human prostate were successfully obtained, enabling quantification of apparent diffusion coefficients (ADCs) in normal and pathologic regions. A dual acquisition fast spin-echo sequence was used for accurate T 2 calculation. T 2 values were significantly higher in the peripheral zone than the central gland (P ؍ 0.015). No significant correlations were found in either normal or pathologic tissue between ADC values and relaxation rates for all three gradient directions and the orientationally averaged water diffusion coefficient. Evidence suggesting that diffusional anisotropy is present in normal prostatic tissue is also detailed, with significant differences noted between the z-component and both the x-and y-components of the ADC for peripheral zone (P < 0.040) and central gland (P < 0.001 Over the past few years MR imaging of the human prostate has become more prevalent. However, due to the similarity in signal intensity between prostatic carcinoma and benign prostatic hyperplasia (BPH) on T 2 -weighted imaging, the usefulness of conventional MRI is reduced, particularly for the 35% of tumors which arise within the central gland (1). It is also recognized that unenhanced MRI can both under-and overestimate tumor volume when compared with pathological specimens. Lencioni et al. (2) obtained volume measurements that were only accurate to within 50% of the pathological volume. A recent review suggested that generalized use of MR imaging for tumor staging was not recommended, although MR did become cost-effective for men with moderate or high prior probability of extracapsular disease (3).Many authors have suggested that the use of dynamic contrast-enhanced imaging may improve delineation between conditions, since neovascularity is an independent indicator of pathological state (4 -7). Significant differences have been noted for various pharmacokinetic parameters, between benign and malignant disease, although patient numbers are often small (6,8). Various workers have explored the further addition of proton MR spectroscopy to improve clinical efficacy. Recently, Swanson et al. (9) have shown the potential of J-resolved spectroscopy of the prostate in obtaining additional physiologic information.An alternative approach may involve the utilization of diffusion-weighted imaging, which has seen increasing clinical relevance in the brain. A high degree of correlation between the trace of the diffusion tensor (Trace[D] and R 2 (1/T 2 ) has been noted during brain maturation in kittens (10). However, studies of stroke and ischemia have shown that there is a rapid decrease in Trace [D] with no detectable changes in T 2 data (11,12). These effects are often attributed to changes in extracellular volume fraction and increased tortuosity of the extracellular space. Good agreement of the histological measurement of infarct size with the total area of decreased apparent diffusion coefficient (ADC) has also been demonstrated in a rat model (11).MR diffusion-weighted imaging h...
A prospective study was undertaken in women undergoing neoadjuvant chemotherapy for locally advanced breast cancer in order to determine the ability of quantitative magnetic resonance imaging (MRI) and proton spectroscopy (MRS) to predict ultimate tumour response (percentage decrease in volume) or to detect early response. Magnetic resonance imaging and MRS were carried out before treatment and after the second of six treatment cycles. Pharmacokinetic parameters were derived from T 1 -weighted dynamic contrast-enhanced MRI, water apparent diffusion coefficient (ADC) was measured, and tissue water : fat peak area ratios and water T 2 were measured using unsuppressed one-dimensional proton spectroscopic imaging (30 and 135 ms echo times). Pharmacokinetic parameters and ADC did not detect early response; however, early changes in water : fat ratios and water T 2 (after cycle two) demonstrated substantial prognostic efficacy. Larger decreases in water T 2 accurately predicted final volume response in 69% of cases (11/16) while maintaining 100% specificity and positive predictive value. Small/absent decreases in water : fat ratios accurately predicted final volume non-response in 50% of cases (3/6) while maintaining 100% sensitivity and negative predictive value. This level of accuracy might permit clinical application where early, accurate prediction of non-response would permit an early change to second-line treatment, thus sparing patients unnecessary toxicity, psychological morbidity and delay of initiation of effective treatment.
Neuroaxonal loss is a major substrate of irreversible disability in multiple sclerosis, however, its cause is not understood. In multiple sclerosis there may be intracellular sodium accumulation due to neuroaxonal metabolic dysfunction, and increased extracellular sodium due to expansion of the extracellular space secondary to neuroaxonal loss. Sodium magnetic resonance imaging measures total sodium concentration in the brain, and could investigate this neuroaxonal dysfunction and loss in vivo. Sodium magnetic resonance imaging has been examined in small cohorts with relapsing-remitting multiple sclerosis, but has not been investigated in patients with a progressive course and high levels of disability. We performed sodium magnetic resonance imaging in 27 healthy control subjects, 27 patients with relapsing-remitting, 23 with secondary-progressive and 20 with primary-progressive multiple sclerosis. Cortical sodium concentrations were significantly higher in all subgroups of multiple sclerosis compared with controls, and deep grey and normal appearing white matter sodium concentrations were higher in primary and secondary-progressive multiple sclerosis. Sodium concentrations were higher in secondary-progressive compared with relapsing-remitting multiple sclerosis in cortical grey matter (41.3 ± 4.2 mM versus 38.5 ± 2.8 mM, P = 0.008), normal appearing white matter (36.1 ± 3.5 mM versus 33.6 ± 2.5 mM, P = 0.018) and deep grey matter (38.1 ± 3.1 mM versus 35.7 ± 2.4 mM, P = 0.02). Higher sodium concentrations were seen in T₁ isointense (44.6 ± 7.2 mM) and T1 hypointense lesions (46.8 ± 8.3 mM) compared with normal appearing white matter (34.9 ± 3.3 mM, P < 0.001 for both comparisons). Higher sodium concentration was observed in T₁ hypointense lesions in secondary-progressive (49.0 ± 7.0 mM) and primary-progressive (49.3 ± 8.0 mM) compared with relapsing-remitting multiple sclerosis (43.0 ± 8.5 mM, P = 0.029 for both comparisons). Independent association was seen of deep grey matter sodium concentration with expanded disability status score (coefficient = 0.24, P = 0.003) and timed 25 ft walk speed (coefficient = -0.24, P = 0.01), and of T1 lesion sodium concentration with the z-scores of the nine hole peg test (coefficient = -0.12, P < 0.001) and paced auditory serial addition test (coefficient = -0.081, P < 0.001). Sodium concentration is increased within lesions, normal appearing white matter and cortical and deep grey matter in multiple sclerosis, with higher concentrations seen in secondary-progressive multiple sclerosis and in patients with greater disability. Increased total sodium concentration is likely to reflect neuroaxonal pathophysiology leading to clinical progression and increased disability.
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