Faculty Bibliography

PURPOSE: To study the feasibility of using the MRI technique of segmented true-fast imaging with steady-state precession arterial spin-labeling (True-FISP ASL) for the noninvasive measurement and quantification of local perfusion in cerebral deep gray matter at 3T. MATERIALS AND METHODS: A flow-sensitive alternating inversion-recovery (FAIR) ASL perfusion preparation was used in which the echo-planar imaging (EPI) readout was replaced with a segmented True-FISP data acquisition strategy. The absolute perfusion for six selected regions of deep gray matter (left and right thalamus, putamen, and caudate) were calculated in 11 healthy human subjects (six male, five female; mean age = 35.5 years +/- 9.9). RESULTS: Preliminary measurements of the average absolute perfusion values at the six selected regions of deep gray matter are in agreement with published values for mean absolute cerebral blood flow (CBF) baselines acquired from healthy volunteers using positron emission tomography (PET). CONCLUSION: Segmented True-FISP ASL is a practical and quantitative technique suitable to measure local tissue perfusion in cerebral deep gray matter at a high spatial resolution without the susceptibility artifacts commonly associated with EPI-based methods of ASL. J. Magn. Reson. Imaging 2009;29:1425-1431. (c) 2009 Wiley-Liss, Inc

Multiple sclerosis (MS) is a disease of the central nervous system characterized by widespread demyelination, axonal loss and gliosis, and neurodegeneration; susceptibility-weighted imaging (SWI), through the use of phase information to enhance local susceptibility or T2* contrast, is a relatively new and simple MRI application that can directly image cerebral veins by exploiting venous blood oxygenation. Here, we use high-field SWI at 3.0 Tesla to image 15 patients with clinically definite relapsing-remitting MS and to assess cerebral venous oxygen level changes. We demonstrate significantly reduced visibility of periventricular white matter venous vasculature in patients as compared to control subjects, supporting the concept of a widespread hypometabolic MS disease process. SWI may afford a noninvasive and relatively simple method to assess venous oxygen saturation so as to closely monitor disease severity, progression, and response to therapy

PURPOSE: To investigate whether the variable forms of putative iron deposition seen with susceptibility weighted imaging (SWI) will lead to a set of multiple sclerosis (MS) lesion characteristics different than that seen in conventional MR imaging. MATERIALS AND METHODS: Twenty-seven clinically definite MS patients underwent brain scans using magnetic resonance imaging including: pre- and postcontrast T1-weighted imaging, T2-weighted imaging, FLAIR, and SWI at 1.5 T, 3 T, and 4 T. MS lesions were identified separately in each imaging sequence. Lesions identified in SWI were reevaluated for their iron content using the SWI filtered phase images. RESULTS: There were a variety of new lesion characteristics identified by SWI, and these were classified into six types. A total of 75 lesions were seen only with conventional imaging, 143 only with SWI, and 204 by both. From the iron quantification measurements, a moderate linear correlation between signal intensity and iron content (phase) was established. CONCLUSION: The amount of iron deposition in the brain may serve as a surrogate biomarker for different MS lesion characteristics. SWI showed many lesions missed by conventional methods and six different lesion characteristics. SWI was particularly effective at recognizing the presence of iron in MS lesions and in the basal ganglia and pulvinar thalamus

Noninvasive measurement of cerebral venous oxygenation can serve as a tool for better understanding fMRI signals and for clinical evaluation of brain oxygen homeostasis. In this study a novel technique, T2-Relaxation-Under-Spin-Tagging (TRUST) MRI, is developed to estimate oxygenation in venous vessels. This method uses the spin labeling principle to automatically isolate pure blood signals from which T2 relaxation times are determined using flow-insensitive T2-preparation pulses. The blood T2 is then converted to blood oxygenation using a calibration plot. In vivo experiments gave a baseline venous oxygenation of 64.8 +/- 6.3% in sagittal sinus in healthy volunteers (n = 24). Reproducibility studies demonstrated that the standard deviation across trials was 2.0 +/- 1.1%. The effects of repetition time and inversion time selections were investigated. The TRUST technique was further tested using various physiologic challenges. Hypercapnia induced an increase in venous oxygenation by 13.8 +/- 1.1%. On the other hand, caffeine ingestion resulted in a decrease in oxygenation by 7.0 +/- 1.8%. Contrast agent infusion (Gd-DTPA, 0.1 mmol/kg) reduced venous blood T2 by 11.2 ms. The results of this study show that TRUST MRI is a useful technique for quantitative assessment of blood oxygenation in the brain

Although BOLD functional MRI (fMRI) provides a useful tool for probing neuronal activities, large intersubject variations in signal amplitude are commonly observed. Understanding the physiologic basis for these variations will have a significant impact on many fMRI studies. First, the physiologic modulator can be used as a regressor to reduce variations across subjects, thereby improving statistical power for detecting group differences. Second, if a pathologic condition or a drug treatment is shown to change fMRI responses, monitoring this modulatory parameter is useful in correctly interpreting the fMRI changes to neuronal deficits/recruitments. Here we present evidence that the task-evoked fMRI signals are modulated by baseline blood oxygenation. To measure global blood oxygenation, we used a recently developed technique, T(2) relaxation under spin-tagging (TRUST) MRI, which yielded baseline oxygenation of 63.7% +/- 7.2% in the sagittal sinus with an estimation error of 1.3%. It was found that individuals with higher baseline oxygenation tend to have a smaller fMRI signal, and vice versa. For every 10% difference in baseline oxygenation across subjects, BOLD and cerebral blood flow (CBF) signals differ by -0.4% and -30.0%, respectively, when using visual stimulation. TRUST MRI is a useful measurement for fMRI studies to control for the modulatory effects of baseline oxygenation that are unique to each subject

BACKGROUND: Although the role of vascular pathology in multiple sclerosis (MS) lesions was suggested long ago, the derivation of these lesions from the vasculature has been difficult to assess in vivo. Ultrahigh-field (eg, 7-T) magnetic resonance imaging (MRI) has become a tool for assessing vascular involvement in MS lesions owing to markedly increased image resolution and susceptibility contrast of venous blood. OBJECTIVE: To describe the perivenous association of MS lesions on high-resolution and high-contrast 7-T susceptibility-sensitive MRI. DESIGN: Case study. SETTING: University hospital. PATIENTS: Two women with clinically definite relapsing-remitting MS. RESULTS: We demonstrated markedly enhanced detection of unique microvascular involvement associated with most of the visualized MS lesions with abnormal signals on and around the venous wall on 7-T compared with 3-T MRI. CONCLUSIONS: These findings, which have never been shown on conventional fields of MRI, not only allow for direct evidence of vascular pathogenesis in MS in vivo but also have important implications for monitoring lesion activity and therapeutic response

Although perfusion is of major interest for many spinal cord disorders, there is no established, reproducible technique for evaluating blood flow or blood volume of the spinal cord in humans. Here the first report of in vivo measurement of human spinal cord blood volume (scBV) is presented. An FDA-approved contrast agent, Gd-DTPA, was used as an intravascular agent for the cord parenchyma, and pre-/post-contrast vascular-space-occupancy (VASO) MRI experiments were performed to obtain a quantitative estimation of scBV in mL blood/100 mL tissue. VASO MRI was used because it does not rely on knowledge of an arterial input function, it avoids the imaging artifacts of single-shot echo planar imaging approaches, and it requires only relatively simple and direct calculations for scBV quantification. Preliminary tests at 1.5 T and 3 T gave mean +/- SD scBV values of 4.3 +/- 0.7 ml/100 mL tissue (n = 6) and 4.4 +/- 0.7 ml/100 mL tissue (n = 4), respectively, consistent with the expectation that the scBV values would not be field-dependent

BACKGROUND AND PURPOSE: Deposition of iron has been recognized recently as an important factor of pathophysiologic change including neurodegenerative processes in multiple sclerosis (MS). We propose that there is an excess accumulation of iron in the deep gray matter in patients with MS that can be measured with a newly developed quantitative MR technique--magnetic field correlation (MFC) imaging. MATERIALS AND METHODS: With a 3T MR system, we studied 17 patients with relapsing-remitting MS and 14 age-matched healthy control subjects. We acquired MFC imaging using an asymmetric single-shot echo-planar imaging sequence. Regions of interest were selected in both deep gray matter and white matter regions, and the mean MFC values were compared between patients and controls. We also correlated the MFC data with lesion load and neuropsychologic tests in the patients. RESULTS: MFC measured in the deep gray matter in patients with MS was significantly higher than that in the healthy controls (P < or = .03), with an average increase of 24% in the globus pallidus, 39.5% in the putamen, and 30.6% in the thalamus. The increased iron deposition measured with MFC in the deep gray matter in the patients correlated positively with the total number of MS lesions (thalamus: r = 0.61, P = .01; globus pallidus: r = 0.52, P = .02). A moderate but significant correlation between the MFC value in the deep gray matter and the neuropsychologic tests was also found. CONCLUSION: Quantitative measurements of iron content with MFC demonstrate increased accumulation of iron in the deep gray matter in patients with MS, which may be associated with the disrupted iron outflow pathway by lesions. Such abnormal accumulation of iron may contribute to neuropsychologic impairment and have implications for neurodegenerative processes in MS

BACKGROUND AND PURPOSE: Hypoperfusion of the normal-appearing white matter in multiple sclerosis (MS) may be related to ischemia or secondary to hypometabolism from wallerian degeneration (WD). This study evaluated whether correlating perfusion and diffusion tensor imaging (DTI) metrics in normal-appearing corpus callosum could provide support for an ischemic mechanism for hypoperfusion. MATERIALS AND METHODS: Fourteen patients with relapsing-remitting MS (RRMS) and 17 control subjects underwent perfusion MR imaging and DTI. Absolute measures of cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) were calculated. Mean diffusivity (MD) and fractional anisotropy (FA) maps were computed from DTI data. After visual coregistration of perfusion and DTI images, regions of interest were placed in the genu, central body, and splenium of normal-appearing corpus callosum. Pearson product-moment correlation coefficients were calculated using mean DTI and perfusion measures in each region. RESULTS: In the RRMS group, CBF and CBV were significantly correlated with MD in the splenium (r = 0.83 and r = 0.63, respectively; both P < .001) and in the central body (r = 0.86 and r = 0.65, respectively; both P < .001), but not in the genu (r = 0.23 and 0.25, respectively; both P is nonsignificant). No significant correlations were found between MTT and DTI measures or between FA and any perfusion measure in the RRMS group. No significant correlations between diffusion and perfusion metrics were found in control subjects. CONCLUSION: In the normal-appearing corpus callosum of patients with RRMS, decreasing perfusion is correlated with decreasing MD. These findings are more consistent with what would be expected in primary ischemia than in secondary hypoperfusion from WD.

Multiple sclerosis (MS) is considered a prototypical inflammatory autoimmune disease of the central nervous system that affects both myelin and axon. One of the most challenging aspects of MS is understanding the nature and mechanism of tissue injury because inflammation, demyelination, axonal degeneration, microvascular injury, and atrophy are all identified in histopathologic studies. Magnetic resonance (MR) imaging provides an in vivo examination of the brain that directly defines the extent of the pathology. In recent years, extensive MR studies have had a major impact on MS not only in making an early diagnosis but also in understanding of the disease. By exploiting the natural history and histopathologic correlation, conventional and various novel quantitative MR techniques have demonstrated the ability to image underlying pathological processes in MS. This review examines the role of different MR techniques in going beyond anatomical imaging and produces a more comprehensive overview of the pathophysiological changes which occur and evolve in MS.