Scoutless stepping-table peripheral contrast-enhanced MR angiography.

PURPOSE: To evaluate the feasibility of a scoutless method, termed EZ-STEP, for stepping-table peripheral contrast-enhanced magnetic resonance angiography (CE-MRA). MATERIALS AND METHODS: This scoutless method involves the use of a stepping-table, fast 3D MRA acquisition that incorporates spatially nonselective radiofrequency (RF) pulses for excitation to reduce the repetition time (TR). The sequence was tested in a phantom. The EZ-STEP protocol was optimized in four healthy volunteers and used in 15 subjects. The image quality was scored in a blinded fashion and compared with conventional MRA in eight patients. RESULTS: The acquisition speed of the EZ-STEP sequence was approximately 30% faster in the phantom study compared to the conventional MRA sequence. The total examination time for EZ-STEP was 6 minutes, compared to an average of 23 minutes for conventional MRA. The average image quality scores for EZ-STEP and conventional MRA for stations 1-3 were 3.50 vs. 3.06 (P = 0.087), 3.53 vs. 3.00 (P = 0.033), and 2.97 vs. 2.50 (P = 0.090), respectively. CONCLUSION: EZ-STEP is a more efficient method than the conventional approach for stepping-table peripheral CE-MRA, and provides comparable or better image quality. This method shortens the examination time substantially and eliminates the risk of failing to image a vessel because of improper positioning of the scan volume.

Effect of free radical scavenger (tempol) on intrarenal oxygenation in hypertensive rats as evaluated by BOLD MRI.

PURPOSE: To demonstrate a differential response following administration of a free radical scavenger, tempol, in kidneys of hypertensive compared to normotensive rats. MATERIAL AND METHODS: Data were obtained in spontaneously hypertensive rats (SHR, N = 5). Wistar-Kyoto rats (WKY, N = 6) were used as normotensive controls. RESULTS: Consistent with prior reports, SHRs show a significant response to tempol (R(2)*decreased from 40.56 +/- 0.66 second(-1) to 28.58 +/- 0.6 second(-1) in medulla, P < 0.05), while WKY rats exhibit a minimal change (R(2)* measuring 22.36 +/- 4.38 second(-1) pre-tempol and 21.57 +/- 4.78 second(-1) post-tempol, in medulla). The post-tempol R(2)* in SHR was found to be comparable to pre-tempol values in WKY rats, suggesting an improved medullary oxygenation in SHRs. CONCLUSION: Based on both baseline R(2)* values and the differential effect of the free radical scavenger on renal medullary oxygenation, BOLD MRI can distinguish hypertensive from normal kidney in rats.

First-pass contrast-enhanced magnetic resonance angiography in humans using ferumoxytol, a novel ultrasmall superparamagnetic iron oxide (USPIO)-based blood pool agent.

PURPOSE: To evaluate the feasibility of first-pass contrast-enhanced magnetic resonance angiography (MRA) using ferumoxytol in humans. MATERIALS AND METHODS: First-pass and equilibrium phase MRA were performed using ferumoxytol in one healthy volunteer and 11 patients with a fast three-dimensional spoiled gradient recalled (SPGR) pulse sequence. The examined vessels included carotid arteries, thoracic aorta, abdominal aorta, and peripheral arteries. A dose of either 71.6 micromol Fe/kg (n = 9), or 35.8 micromol Fe/kg (n = 3) was used. Based on a phantom study, the agent with initial concentration of 537.2 micromol Fe/mL was diluted by either four-fold (134.3 micromol Fe/mL) or eight-fold (67.1 micromol Fe/mL) for first-pass MRA. RESULTS: All subjects completed their studies without adverse events. First-pass MRA showed selective arterial enhancement, with both arterial and venous enhancement on delayed acquisitions. Selective venous enhancement could be obtained by subtraction of arterial phase images from equilibrium phase images. The findings in ferumoxytol MRA were consistent with the results of original vascular tests. CONCLUSION: Our preliminary experience supports the feasibility of first-pass MRA with ferumoxytol. Satisfactory arterial enhancement during first-pass imaging is obtained with injection of diluted contrast agent. With ferumoxytol, arteries and veins can be selectively depicted in a single exam.

Relapsing-remitting multiple sclerosis: metabolic abnormality in nonenhancing lesions and normal-appearing white matter at MR imaging: initial experience.

PURPOSE: To quantify, with three-dimensional proton magnetic resonance (MR) spectroscopy, metabolic characteristics of normal-appearing white matter and nonenhancing lesions in patients with relapsing-remitting multiple sclerosis (MS). MATERIALS AND METHODS: Institutional review board approval and informed patient consent were obtained. Nine patients with relapsing-remitting MS (six women, three men) and nine age-matched control subjects (seven women, two men) were studied with T1- and T2-weighted MR imaging and three-dimensional proton MR spectroscopy at spatial resolution less than a cubic centimeter. Absolute N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) levels were obtained from 171 voxels: 66 from lesions on T2-weighted MR images (43 hypointense and 23 isointense on T1-weighted MR images), 31 from normal-appearing white matter, and 74 from analogous normal white matter regions on images in control subjects. RESULTS: Mean NAA level in hypointense lesions (5.30 mmol/L +/- 2.27 [standard deviation]) was significantly lower (P < or = .05) than that in isointense lesions (7.82 mmol/L +/- 2.28), normal-appearing white matter (7.37 mmol/L +/- 1.71), and normal white matter in control subjects (8.89 mmol/L +/- 1.54). Cho (1.79 mmol/L +/- 0.65) and Cr (5.64 mmol/L +/- 1.50) levels in isointense lesions were indistinguishable from those in normal-appearing white matter (1.74 mmol/L +/- 0.46 and 4.99 mmol/L +/- 0.97, respectively) but were significantly higher (Cho, 20%; Cr, 24%) than those in normal white matter in control subjects (1.44 mmol/L +/- 0.40 and 4.30 mmol/L +/- 1.32, respectively). NAA, Cho, and Cr levels in normal-appearing white matter were significantly different than those in normal white matter in control subjects (NAA, 20% lower; Cho, 14% higher; and Cr, 17% higher). CONCLUSION: Abnormal metabolic activity persists in all MS tissue types. Increased Cr and Cho levels suggest (a) ongoing gliosis and attempted remyelination in isointense lesions on T1-weighted MR images and (b) membrane turnover (de- and remyelination), in addition to increased cellularity (gliosis, inflammation) in normal-appearing white matter.

Evaluation of intrarenal oxygenation by BOLD MRI at 3.0 T.

PURPOSE: To examine the benefit of using higher field strengths for BOLD MRI to detect changes in renal medullary oxygenation following pharmacological maneuvers. MATERIALS AND METHODS: Renal BOLD MRI, primarily at 1.5 T, has been shown to be useful for monitoring changes in medullary oxygenation status. We performed the present studies on a 3.0 T scanner using a multiple gradient-echo (mGRE) sequence with a multicoil array to acquire 16 T2*-weighted images within a single breath-hold. Data were obtained before and after administration of furosemide (20 mg iv). RESULTS: The baseline renal R2* (mean +/- SE) at 3.0 T was 37.4+/-1.2 Hz in the medulla, and 21.8 +/- 1.2 Hz in the cortex. The BOLD response to furosemide (DeltaR2*) at 3.0 T was 11.8 +/- 1.1 Hz in the medulla, and 3.0 +/- 0.5 Hz in the cortex. CONCLUSION: Higher magnetic field strength is beneficial for renal BOLD MRI studies. The cortico-medullary contrast on the R2* map was significantly improved at 3.0 T, with no evidence of increased bulk susceptibility artifacts. Baseline R2* and DeltaR2* in the renal medulla at 3.0 T were both significantly higher compared to our previously reported data obtained at 1.5 T.

Myocardial delayed enhancement imaging using inversion recovery single-shot steady-state free precession: initial experience.

PURPOSE: To evaluate the feasibility of using an inversion recovery single-shot steady-state free precession (SS_SSFP) sequence for myocardial delayed enhancement (MDE) imaging, and to compare SS_SSFP with the conventional inversion recovery segmented fast gradient echo (IR_FGRE) technique. MATERIALS AND METHODS: Ten subjects (four volunteers and six patients with suspected or known coronary disease) were included in this study. All subjects were scanned with both IR_FGRE and SS_SSFP sequences 15-25 minutes after gadopentetate dimeglumine injection. Overall image quality, signal-to-noise ratios (SNRs), and contrast-to-noise ratios (CNRs) between the two techniques were compared. RESULTS: Compared to IR_FGRE, SS_SSFP exhibited adequate image quality (average scores = 3.8 for IR_FGRE and 3.9 for SS_SSFP) with much shorter acquisition time (14.4 seconds for IR_FGRE and 1.3 seconds for SS_SSFP). SS_SSFP images showed higher SNRs (P < 0.05) and less motion artifact from breathing. Enhanced myocardium was detected by both techniques in three patients, but the image sharpness is compromised in SS_SSFP images. CONCLUSION: SS_SSFP provides adequate image quality compared to IR_FGRE, while requiring a much shorter acquisition time. It is feasible to use SS_SSFP as an alternative method for MDE imaging, especially in patients who have difficulty with holding their breath.

Dark flow artifacts with steady-state free precession cine MR technique: causes and implications for cardiac MR imaging.

Steady-state free precession cine images from cardiac magnetic resonance imaging studies of 24 patients were reviewed retrospectively to identify dark flow artifacts. The cause and features of the artifacts were studied in flow phantom experiments. Dark flow artifacts were recognized in eight of the 24 cases and were characterized by low or inhomogeneous signal intensity in blood pools with little change in adjacent tissues. The artifacts could be mimicked in flow phantom experiments by deliberately deshimming the gradients and appeared periodically during imaging with off-centered frequencies. These artifacts appeared to be caused by spins moving within an inhomogeneous magnetic field.

Metabolite ratios to assumed stable creatine level may confound the quantification of proton brain MR spectroscopy.

In localized brain proton MR spectroscopy ((1)H-MRS), metabolites' levels are often expressed as ratios, rather than as absolute concentrations. Frequently, their denominator is the creatine [Cr], which level is explicitly assumed to be stable in normal as well as in many pathologic states. The rationale is that ratios self-correct for imager and localization method differences, gain instabilities, regional susceptibility variations and partial volume effects. The implicit assumption is that these benefits are worth their cost(w)-(w) propagation of the individual variation of each of the ratio's components. To test this hypothesis, absolute levels of N-acetylaspartate [NAA], choline [Cho] and [Cr] were quantified in various regions of the brains of 8 volunteers, using 3-dimensional (3D) (1)H-MRS at 1.5 T. The results show that in over 50% of approximately 2000 voxels examined, [NAA]/[Cr] and [Cho]/[Cr] exhibited higher coefficients of variations (CV) than [NAA] and [Cho] individually. Furthermore, in approximately 33% of these voxels, the ratios' CVs exceeded even the combined constituents' CVs. Consequently, basing metabolite quantification on ratios and assuming stable [Cr] introduces more variability into (1)H-MRS than it prevents. Therefore, its cost exceeds the benefit.

Diffusely elevated cerebral choline and creatine in relapsing-remitting multiple sclerosis.

It is well known that multiple sclerosis (MS) pathogenesis continues even during periods of clinical silence. To quantify the metabolic characteristics of this activity we compared the absolute levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho) in the normal-appearing white matter (NAWM) between relapsing-remitting (RR) MS patients and controls. Metabolite concentrations were obtained with 3D proton MR spectroscopy at 1.5 T in a 480 cm(3) volume-of-interest (VOI), centered on the corpus callosum of 11 MS patients and 9 matched controls. Gray/white-matter/cerebral-spinal-fluid (CSF) volumes were obtained from MRI segmentation. Patients' average VOI tissue volume (V(T)), 410.8 +/- 24.0 cm(3), and metabolite levels, NAA = 6.33 +/- 0.70, Cr = 4.67 +/- 0.52, Cho = 1.40 +/- 0.17 mM, were different from the controls by -8%, -9%, +22% and +32%. The Cho level was the only single metric differentiating patients from controls at 100% specificity and >90% sensitivity. Diffusely elevated Cho and Cr probably reflect widespread microscopic inflammation, gliosis, or de- and remyelination in the NAWM. Both metabolites are potential prognostic indicators of current disease activity, preceding NAA decline and atrophy.

Brain metabolite profiles of T1-hypointense lesions in relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: Persistent T1-hypointense lesions ("black holes") are thought to represent permanent damage of brain parenchyma. We attempted to ascertain whether the metabolic profiles of these hypointense areas support this hypothesis and whether these profiles correlate with these hypointense findings. METHODS: Four patients with relapsing-remitting multiple sclerosis and four matched control volunteers underwent MR imaging and 3D proton MR spectroscopy. Absolute levels of N-acetylaspartate (NAA), creatine, and choline (Cho) were obtained in 0.19 cm(3) voxels containing 14 T1-hypointense lesions (average volume, 0.4 cm(3); range, 0.2-1.0 cm(3)) in patients. Metabolite levels were analyzed, by using Pearson correlation, against their respective lesions' hypointensity relative to the surrounding normal-appearing white matter. RESULTS: Moderate correlation, r = 0.56, was found between the NAA level and MR imaging hypointensity. Of the 14 lesions studied, 12 were deficient in NAA and 11 had excess Cho compared with corresponding brain regions in control volunteers. Only one lesion was significantly deficient in all three metabolites, indicative of total damage or matrix loss. CONCLUSION: No relationship was found between the hypointensity of the lesions and their metabolic profile. Specifically, lesions with the same hypointensity on T1-weighted MR images were metabolically variable (ie, displayed disparate metabolite levels and behavior). Also, although 86% of the lesions exhibited abnormally low NAA, 71% also had increased Cho. This indicates that although neuronal damage had already occurred (lower NAA), these lesions were still "smoldering" with active membrane turnover (high Cho), most likely because of de- and remyelination, indicative of shadow plaques (remyelinated lesions). Consequently, relapsing-remitting hypointense lesions represent neither final-stage nor static pathologic abnormality.

Relapsing-remitting multiple sclerosis and whole-brain N-acetylaspartate measurement: evidence for different clinical cohorts initial observations.

PURPOSE: To quantify the rate of concentration decline of neuronal marker N-acetylaspartate (NAA) in the entire brain of patients with relapsing-remitting multiple sclerosis (MS) in relation to healthy age-matched control subjects. MATERIALS AND METHODS: Whole-brain NAA (WBNAA) concentration was quantified in 49 patients with relapsing-remitting MS by using magnetic resonance (MR) imaging and proton MR spectroscopy. It was statistically analyzed by using Spearman rank correlation coefficients to test the intragroup relationship between WBNAA and Expanded Disability Status Scale (EDSS) score and Mann-Whitney analyses to test for differences between subgroups' EDSS scores versus previously published WBNAA values for healthy subjects, disease duration, and age. RESULTS: Analyses indicated three subgroups of WBNAA dynamics: Ten patients' conditions were "stable," exhibiting an insignificant change of about 0% (0.02/14.37) per year of clinically definite disease duration (P =.54); 27 patients showed "moderate" decline, -2.8% (-0.34/12.18) per year (P <.01); and 12 patients experienced "rapid" decline, -27.9% (-3.39/12.14) per year (P <.01). No correlation was found between WBNAA deficit, EDSS score, and age. CONCLUSION: Ascertaining an individual's NAA concentration dynamics might enable early forecast of disease course, reflect disease severity and thus influence treatment decisions, and improve clinical trial efficiency by allowing selection of candidates on the basis of WBNAA dynamics in addition to clinical status.

Whole-brain N-acetylaspartate concentration: correlation with T2-weighted lesion volume and expanded disability status scale score in cases of relapsing-remitting multiple sclerosis.

BACKGROUND AND PURPOSE: The T2-weighted MR imaging total lesion volume and Expanded Disability Status Scale (EDSS) score are two common measures of relapsing-remitting multiple sclerosis disability and pathologic abnormality. Because the whole-brain N-acetylaspartate concentration is considered to be a new marker of the disease burden, the purpose of this study was to evaluate the relationship among these three measures. METHODS: The whole-brain N-acetylaspartate concentration and T2-weighted lesion volume were quantified by using MR imaging and proton MR spectroscopy in 49 patients with relapsing-remitting multiple sclerosis (36 female and 13 male patients; average age, 39 years; age range, 24-55 years; average EDSS score, 2; range of EDSS scores, 0-6). Correlations among whole-brain N-acetylaspartate concentrations, T2-weighted lesion volumes, and EDSS scores were obtained. RESULTS: No correlation was found between whole-brain N-acetylaspartate levels and either T2-weighted lesion volumes or EDSS scores. A weak correlation was found between the EDSS scores and T2-weighted lesion volumes (P =.043, r(s) = 0.292). CONCLUSION: Despite the lack of correlation between whole-brain N-acetylaspartate concentration and the clinical disability reflected in the EDSS score, only the former evaluates the global neuronal cell disease in the entire brain, including those lesions that are occult to conventional imaging techniques.

Reproducibility of 3D proton spectroscopy in the human brain.

The inter- and intrasubject reproducibility of the metabolite levels of N-acetylaspartate (NAA), creatine (Cr), and choline (Cho), obtained with three-dimensional (3D) multivoxel proton spectroscopy (1H-MRS), was analyzed in eight healthy volunteers. Serial, back-to-back measurements on a phantom showed the methodology and instrumentation to be highly reproducible, with a median coefficient of variation (CV) of 3.8%. In the human brain, the metabolite levels' variability was larger, with intrasubject median CVs for a total of 1876 signal voxels of 13.8%, 18.5%, and 20.1% for NAA, Cr, and Cho, respectively. These variations possibly arise from small, unavoidable, +/-1-2 mm volume-of-interest (VOI) repositioning uncertainties, which vary each 0.75-cm(3) voxel's partial fluid/gray/white-matter fractions. Comparing the CVs between eight subjects in a total of 324 selected voxels gave total interindividual CVs of 15.6%, 23.3%, and 24.4%, compared with intraindividual CVs in the same voxels of 14.4%, 14.8%, and 15.3%, for NAA, Cr, and Cho, respectively. Replacing the signal(s) from each voxel by the average of itself with its six canonical neighbors reduces the intrasubject median CVs to 8.3%, 9.5%, and 9.7%. The measurement uncertainties can be reduced at a cost of either spatial resolution (by using larger voxels) or time (by performing serial follow-ups).