Patterns of lesion development in multiple sclerosis: longitudinal observations with T1-weighted spin-echo and magnetization transfer MR.

PURPOSEWe evaluated the appearance of enhancing multiple sclerosis (MS) lesions on unenhanced T1-weighted MR images and the natural course of enhancing MS lesions on serial unenhanced T1-weighted and magnetization transfer (MT) MR images.METHODSOne hundred twenty-six enhancing lesions were followed up monthly for 6 to 12 months to determine their signal intensity on unenhanced T1-weighted and MT MR images. At the time of initial enhancement, the size of the lesion and the contrast ratio of enhancement were calculated for each enhancing lesion. During follow-up, the contrast ratio on the corresponding unenhanced T1-weighted image was measured, and an MT ratio (MTR) was calculated.RESULTSTwenty-five enhancing lesions (20%) appeared isointense and 101 lesions (80%) appeared hypointense relative to normal-appearing white matter on unenhanced T1-weighted images. During 6 months of follow-up, four MR patterns of active lesions were detected: initially isointense lesions remained isointense (15%); initially isointense lesions became hypointense (5%, most of which reenhanced); initially hypointense lesions became isointense (44%); and initially hypointense lesions remained hypointense (36%). MTR was significantly lower for hypointense lesions as compared with isointense lesions at the time of initial enhancement. For lesions that changed from hypointense to isointense, MTR increased significantly during 6 months of follow-up. Multiple regression analysis showed that strongly decreased MTR at the time of initial enhancement and enhancement duration of more than one scan were predictive of a hypointense appearance on unenhanced T1-weighted images at 6 months'' follow-up. Ring enhancement was found to be the only (weak) predictor of persistently hypointense signal intensity.CONCLUSIONMost enhancing lesions appear slightly to significantly hypointense on unenhanced T1-weighted images. Although most hypointensities are reversible, only those lesions that fail to recover on unenhanced T1-weighted and MT images may have considerable irreversible structural changes.     

Correlation of multiple sclerosis measures derived from T2-weighted, T1-weighted, magnetization transfer, and diffusion tensor MR imaging

BACKGROUND AND PURPOSE: In multiple sclerosis (MS), the severity of tissue damage can vary from edema and inflammation to irreversible demyelination and axonal loss. Compared with conventional T2-weighted MR imaging, magnetization transfer (MT) and diffusion tensor (DT) MR imaging provide quantitative indices with increased specificity to the most destructive aspects of MS. To increase our understanding of the pathophysiologic processes of MS, we assessed the correlations between MT and DT MR imaging-derived metrics and the correlations between these quantities and measures derived from conventional MR in patients with MS. METHODS: T2-weighted, T1-weighted, MT, and DT MR images of the brain were obtained from 34 patients with relapsing-remitting MS (RRMS) and 15 age-matched control subjects. T2 and T1 lesion volumes (LV) and brain volume were measured. MT ratio (MTR), mean diffusivity (D macro), and fractional anisotropy (FA) histograms from the overall brain tissue (BT) and the normal-appearing brain tissue (NABT) were obtained. Average lesion MTR, D macro, and FA were also calculated. The correlations between T2 and T1 LV, brain volume, MT-, and DT-derived metrics were assessed with the Spearman rank correlation coefficient. RESULTS: No significant correlations were found between MT and FA histogram-derived metrics and quantities derived from conventional MR scans (T2 and T1 LV and brain volume). On the contrary, T2 and T1 LV (but not brain volume) were significantly correlated with the average D macro values of BT and NABT (r values ranging from 0.52 to 0.78). No significant correlation was found between MT- and DT-derived metrics. CONCLUSION: These results suggest that MT and DT MR imaging provide, at least partially, independent measures of lesion burden in patients with RRMS. This suggests that a multiparametric MR approach has the potential for increasing our ability to monitor MS evolution.     

T1-weighted three-dimensional magnetization transfer MR of the brain: improved lesion contrast enhancement.

PURPOSEWe developed and evaluated clinically T1-weighted three-dimensional gradient-echo magnetization transfer (MT) sequences for contrast-enhanced MR imaging of the brain.METHODSA short-repetition-time, radio frequency-spoiled, 3-D sequence was developed with a 10-millisecond MT pulse at high MT power and narrow MT pulse-frequency offset, and the enhancing lesion-to-normal white matter background (L/B) and the contrast-to-noise (C/N) ratios on these images were compared with those on T1-weighted spin-echo images and on non-MT 3-D gradient-echo images in a prospective study of 45 patients with 62 enhancing lesions. In the 24 patients who had intracranial metastatic disease, the number of lesions was counted and compared on the three types of images.RESULTSThe MT ratio of normal callosal white matter was 55% on the MT 3-D gradient-echo sequences. The L/B and C/N on the MT 3-D gradient-echo images were more than double those on the 3-D gradient-echo images, and were significantly greater than those on the T1-weighted spin-echo images. In patients with metastatic disease, the MT 3-D gradient-echo images showed significantly more lesions than did the T1-weighted spin-echo or 3-D gradient-echo images.CONCLUSIONMT 3-D gradient-echo MR imaging improves the contrast between enhancing lesion and background white matter over that obtained with conventional T1-weighted 3-D gradient-echo and spin-echo imaging. MT 3-D gradient-echo imaging provides practical sampling, image coverage, and spatial resolution, attributes that may be advantageous over MT T1-weighted spin-echo techniques.     

Multiple sclerosis: magnetization transfer MR imaging of white matter before lesion appearance on T2-weighted images

PURPOSE: To determine the evolution of magnetization transfer (MT) in white matter regions before and after plaque development in patients with multiple sclerosis (MS). MATERIALS AND METHODS: In a 5-year longitudinal evaluation, 30 patients with MS underwent conventional magnetic resonance (MR) imaging, MT MR imaging, and clinical assessment. Cross-sectional data in 12 healthy subjects were also collected. Semiautomated lesion classification with use of T2-weighted MR images was used to measure the time course of the MT ratio (calculated with MR data acquired without and with MT saturation) in every voxel and to help analyze the relationship with the status of lesions depicted on T2-weighted images. RESULTS: There was a significant (P <.001) temporal decline in lesion MT ratio after lesion appearance on T2-weighted images. A significant (P <. 001) progressive decline in MT ratio was also present in voxels that later became lesions, prior to initial detection on T2-weighted images. Even 1(1/2) years prior to lesion appearance, the MT ratio (33.3%) in regions destined to become such lesions was significantly (P <.001) lower than that in both white matter in healthy subjects (41.3%) and other normal-appearing white matter in patients with MS (38.1%). CONCLUSION: The MT ratio reveals progressive focal abnormalities in MS that antedate by up to 2 years the appearance of lesions on T2-weighted MR images.     

Evolution of multiple sclerosis lesions on serial contrast-enhanced T1-weighted and magnetization-transfer MR images

BACKGROUND AND PURPOSE: Magnetization-transfer imaging is a technique that could provide indirect evidence of the characteristics of multiple sclerosis (MS) lesions. The purpose of this work was to study the evolution of MS lesions on T1-weighted MR images over time and to investigate changes in magnetization-transfer ratio (MTR) values of MS lesions with different initial appearances on contrast-enhanced T1-weighted images. METHODS: Eleven patients with relapsing-remitting MS were studied with MR imaging. The MTRs were calculated for 47 lesions that had been classified according to their appearance on contrast-enhanced T1-weighted images. Each patient was examined at four time points over a 1-year period. The MTR changes observed in the selected lesions were compared with their initial T1-weighted appearance. RESULTS: The lowest MTR values were initially found in hypointense nonenhancing lesions and in ring-enhancing lesions, with both types showing a hypointense center. Changes in MTR values were more dynamic and reversible in ring-enhancing than in hypointense nonenhancing plaques. Nodular-enhancing lesions had slightly lower initial MTRs than did isointense non-enhancing lesions. CONCLUSION: The absence or presence of contrast uptake may indicate a different pathologic basis for hypointense MS lesions on T1-weighted MR images. These differences should be kept in mind when considering T1 lesion load as a surrogate marker of disability in MS.     

Detection of corticospinal tract compromise in amyotrophic lateral sclerosis with brain MR imaging: relevance of the T1-weighted spin-echo magnetization transfer contrast sequence

BACKGROUND AND PURPOSE: Hyperintensity in the posterior limb of the internal capsule at T2-weighted MR imaging, consistent with corticospinal tract (CST) degeneration, is described in amyotrophic lateral sclerosis (ALS). However, the lack of specific tests or biological markers hinders confirmation of the diagnosis, especially in the early stages. We investigated the CST in ALS with MR imaging. METHODS: We examined 25 patients (14 men, 11 women; mean age, 49.1 years; range, 29-68 years) and 21 age- and sex-matched control subjects without upper motor neuron signs. According to the revised El Escorial criteria, 22 patients had definite ALS; two, probable ALS; and one, suspected ALS. Fluid-attenuated inversion recovery (FLAIR; TR/TE/TI, 11,000/140/2600) and T1-weighted spin-echo (SE)/magnetization transfer contrast-enhanced (MTC; TR/TE, 510/12) imaging was performed at 1 T. Two experienced neuroradiologists blinded to the patients' history independently evaluated the CST. RESULTS: T1-weighted SE MTC imaging allowed visualization of the CST in both patients and control subjects. T1-weighted SE MTC images showed hypointensity along the CST and bilateral subcortical regions of the precentral gyri in all control subjects and hyperintensity in 80% of patients with ALS (P < .05). FLAIR images showed hyperintensity in these areas in both groups, with no significant difference. CONCLUSION: T1-weighted SE MTC imaging is sensitive and accurate in depicting CST lesions in ALS, whereas FLAIR imaging is not. T1-weighted SE MTC imaging is useful in diagnosing ALS by showing hyperintense areas along the CST, which separates patients from control subjects. This sequence should be included in the workup of patients with weakness and pyramidal signs.     

Proton MR spectroscopy of gadolinium-enhanced multiple sclerosis plaques.

Magnetic resonance (MR) imaging and proton MR spectroscopy were performed in 14 patients with clinically definite multiple sclerosis (MS). Prominent resonances in the 0.5-2.0-ppm region were seen in the spectra of six of nine gadopentetate dimeglumine-enhanced plaques in seven patients. These resonances were presumed to originate in lipids and other myelin breakdown products. Similar resonances were detected in only seven of 21 unenhancing plaques. The more frequent presence of such signals in the gadolinium-enhanced regions indicates that myelin breakdown is often associated with the inflammation that occurs in early stages of MS plaque evolution. It remains uncertain, however, whether active inflammation as indicated by gadolinium enhancement is a necessary precursor of myelin breakdown as detected at MR spectroscopy. Quantitative spectral analysis did not indicate statistically significant differences in N-acetyl aspartate and choline levels relative to creatine plus phosphocreatine between healthy volunteers and MS patients.     

Single-dose gadolinium with magnetization transfer versus triple-dose gadolinium in the MR detection of multiple sclerosis lesions.

PURPOSETo compare the efficacy of single-dose gadolinium with magnetization transfer contrast (MTC) with that of triple-dose gadolinium in detecting enhancing multiple sclerosis lesions.METHODSTwenty-one patients with multiple sclerosis were examined with MR imaging first with 0.1 mmol/kg gadolinium (single dose) and then, after 24 to 72 hours, with 0.3 mmol/kg gadolinium (triple dose). T2-weighted fast spin-echo and T1-weighted spin-echo MR images with and without MTC were obtained before contrast administration followed by either T1-weighted spin-echo images with MTC (single dose) or conventional T1-weighted spin-echo images (triple dose), starting 5, 17, and 29 minutes after contrast administration. All images were evaluated in a blinded fashion and scored in random order by two readers. Outcome parameters included number of enhancing lesions, number of active MR examinations (those containing at least one enhancing lesion), contrast ratio (signal intensity of enhancing lesion divided by signal intensity of normal-appearing white matter), and size of enhancing lesions.RESULTSEighty-one percent more enhancing lesions and 49% more active MR examinations were detected when a triple dose of gadolinium was used as compared with a single dose. The level of agreement between readers as to the number of enhancing lesions was significantly higher for triple-dose than for single-dose gadolinium. With triple-dose gadolinium, contrast ratios and areas of enhancement increased by 10% and 33%, respectively. Delayed imaging increased the size of the lesion by 11% on single-dose MTC images and by 18% on triple-dose images.CONCLUSIONTriple-dose gadolinium is more effective (higher sensitivity and interobserver agreement) than single-dose gadolinium in combination with MTC in detecting enhancing multiple sclerosis lesions.     

Volume T1-weighted gradient echo MRI in multiple sclerosis patients.

Three-dimensional (3D) volume turbo fast low angle shot (FLASH) techniques have become available which produce heavily T1-weighted images, similar to inversion recovery scans, utilizing the appropriate flip angle and inversion time. The purpose of this study was to compare the sensitivity of a rapid volume gradient echo technique [3D magnetization prepared rapid acquisition gradient echo (MP RAGE)] in identifying multiple sclerosis (MS) plaques with a conventional T2-weighted spin echo (SE) sequence. Ten patients with clinical MS were evaluated. Patients underwent a routine examination consisting of an axial T2-weighted SE sequence (2,500,22/90) and a coronal 3D MP RAGE, 10/4/10, acquired as 128 two mm partitions. In six patients, area measurements of 22 plaques were determined on both the axial T2-weighted SE examinations and the axial reformatted MP RAGE examinations. The overall number of plaques utilizing each technique was approximately the same. One hundred twenty-two plaques were visualized for the 3D MP RAGE sequence, and 128 plaques for the T2-weighted SE sequence. There were differences in detection of plaques in different regions, with plaques in gray matter better demonstrated utilizing the conventional T2-weighted SE sequence. Plaques in the corpus callosum, pons, and brachia pontis were better demonstrated utilizing 3D MP RAGE. No significant difference was found between the areas measured on the MP RAGE sequence and on the T2-weighted SE sequence. Three-dimensional MP RAGE provides a sensitive and complementary method to conventional T2-weighted SE sequences in the evaluation of patients with MS.     

Quantification of magnetization transfer rate and native T1 relaxation time of the brain: correlation with magnetization transfer ratio measurements in patients with multiple sclerosis

The purpose of this paper is to perform quantitative measurements of the magnetization transfer rate (Kfor) and native T1 relaxation time (T1free) in the brain tissue of normal individuals and patients with multiple sclerosis (MS) by means of multiple gradient echo acquisitions, and to correlate these measurements with the magnetization transfer ratio (MTR). Quantitative magnetization transfer imaging was performed in five normal volunteers and 12 patients with relapsing–remitting MS on a 1.5 T magnetic resonance (MR) scanner. The T1 relaxation time under magnetization transfer irradiation (T1sat) was calculated by means of fitting the signal intensity over the flip angle in several 3D spoiled gradient echo acquisitions (3°, 15°, 30°, and 60°), while a single acquisition without MT irradiation (flip angle of 3°) was utilized to calculate the MTR. The Kfor and T1free constants were quantified on a pixel-by-pixel basis and parametric maps were reconstructed. We performed 226 measurements of Kfor, T1free, and the MTR on normal white matter (NWM) of healthy volunteers (n=50), and normal-appearing white matter (NAWM) and pathological brain areas of MS patients (n=120 and 56, respectively). Correlation coefficients between Kfor–MTR, T1free–MTR, and T1free–Kfor were calculated. Lesions were classified, according to their characteristics on T1-weighted images, into isointense (compared to white matter), mildly hypointense (showing signal intensity lower than white matter and higher than gray matter), and severely hypointense (revealing signal intensity lower than gray matter). Dirty white matter (DWM) corresponded to areas with diffused high signal, as identified on T2-weighted images. Strong correlation coefficients were obtained between MTR and Kfor for all lesions studied (r²=0.9, p<0.0001), for mildly hypointense plaques (r²=0.82, p<0.0001), and for DWM (r²=0.78, p=0.0007). In contrast, comparison between MTR and T1free values yielded rather low correlation coefficients for all groups assessed. In severely hypointense lesions, an excellent correlation was found between Kfor and T1free measurements (r²=0.98, p<0.0001). Strong correlations between Kfor and T1free were found for the rest of the subgroups, except for the NAWM, in which a moderate correlation was obtained (r²=0.5, p<0.0001). We conclude that Kfor and T1free measurements are feasible and may improve our understanding of the pathological brain changes that occur in MS patients.     

Magnetization transfer effects in MR-detected multiple sclerosis lesions: comparison with gadolinium-enhanced spin-echo images and nonenhanced T1-weighted images.

PURPOSETo define the relationship between magnetization transfer and blood-brain-barrier breakdown in multiple sclerosis lesions using gadolinium enhancement as an index of the latter.METHODSTwo hundred twenty lesions (high-signal abnormalities on T2-weighted images) in 35 multiple sclerosis patients were studied with gadolinium-enhanced spin-echo imaging and magnetization transfer. Lesions were divided into groups having nodular or uniform enhancement, ring enhancement, or no enhancement after gadolinium administration. For 133 lesions, T1-weighted images without contrast enhancement were also analyzed. These lesions were categorized as isointense or hypointense based on their appearance on the unenhanced T1-weighted images.RESULTSThere was no difference between the magnetization transfer ratio (MTR) of lesions as a function of enhancement. MTR of hypointense lesions on unenhanced T1-weighted images was, however, lower than the MTR of isointense lesions.CONCLUSIONWe speculate that diminished MTR may reflect diminished myelin content and that hypointensity on T1-weighted images corresponds to demyelination. Central regions of ring-enhancing lesions had a lower MTR than the periphery, suggesting that demyelination in multiple sclerosis lesions occurs centrifugally. In addition, the short-repetition-time pulse sequence seems useful in the evaluation of myelin loss in patients with multiple sclerosis.     

Evaluation of Gd-enhancement in brain MR of multiple sclerosis: image subtraction with and without magnetization transfer

The aim of our study was to test the possibility of using image subtraction in detecting enhancing lesions in brain MR scans with and without magnetization transfer (MT) in multiple sclerosis (MS). Ten MS patients underwent 1.5-T MR imaging of the brain with spin-echo T1-weighted sequences with and without MT, repeated after 0.1 mmol/kg of an usual two-compartment paramagnetic contrast agent (Gadoteridol, Gd-HP-DO3A). Precontrast images were subtracted from postcontrast. Enhancing lesions were counted on the postcontrast images only (post-Gd), comparing pre- and postcontrast images by direct visual control (pre/post-Gd), and on the subtracted images (SI) only. Without MT, 36 enhancing lesions were counted on post-Gd, 36 on pre/post-Gd, and 59 on SI; using MT, 69, 52, and 50, respectively. Significant differences were found for pre/post-Gd without MT vs SI without MT ( p=0.028) and vs pre/post-Gd with MT ( p=0.012) as well as for pre/post-Gd with MT vs post-Gd with MT ( p=0.028). With pre/post-Gd, MT allowed the detection of 1.6 enhancing lesions per patient more than without MT. Whereas the SI without MT allow the detection of an increased number of enhancing lesions, SI with MT do not. An off-site final assessment allowed calculation of sensitivity and positive predictive value as follows: without MT were 63 and 94% (post-Gd), 67 and 100% (pre/post-Gd), 96 and 88% (SI); and with MT were 93 and 73% (post-Gd), 96 and 100% (pre/post-Gd), 91 and 98% (SI), respectively. Thus, SI seem to increase the sensitivity without MT; moreover, they could be used to correct the pseudoenhancement that impair post-Gd images with MT.     

Measurement of abdominal fat with T1-weighted MR images.

The cross-sectional area of visceral and subcutaneous fat in the abdomen was measured with T1-weighted spin-echo images acquired with a 1.5-T magnetic resonance (MR) imager. Four axial images centered on L-4 were acquired in each patient. Outline regions of interest (ROIs) were drawn manually for subcutaneous and visceral fat. The subcutaneous fat cross-sectional area was calculated from the ROIs drawn around the outer and inner margins of subcutaneous fat. Several adaptive processing methods were evaluated for measuring fat in the complex structure of the viscera. These methods were compared with an existing MR imaging measurement method for abdominal fat in 18 patients. The adaptive method that uses the valley between the fat and nonfat distributions in the average histogram curve was judged best for research evaluations because it reduces the effects of volume averaging while using a more natural division between fat and nonfat data. Another adaptive method that yielded comparable measurements was thought to be more suitable for clinical applications. Cross-sectional area measurements of abdominal fat were compared in 18 nonobese and 17 obese women to illustrate the utility of these measurements.     

Characteristics and pitfalls of contrast-enhanced, T1-weighted magnetization transfer images of the brain

RATIONALE AND OBJECTIVES: This study was undertaken to clarify the difference in signal pattern on contrast material-enhanced T1-weighted magnetic resonance (MR) magnetization transfer (MT) images between enhancing and nonenhancing lesions in various intracranial diseases and to determine the necessity of nonenhanced MT images for evaluating lesional contrast enhancement. MATERIALS AND METHODS: MR images of 116 patients who underwent nonenhanced T1-weighted imaging, nonenhanced MT imaging, and contrast-enhanced MT imaging were reviewed. The increase in signal intensity of lesions relative to normal brain was compared between nonenhanced T1-weighted images and contrast-enhanced MT images. Signal intensity of lesions was compared with that of the striate nucleus and white matter on contrast-enhanced MT images. True enhancement was determined by comparison with nonenhanced MT images. RESULTS: In all, 143 lesions, including 86 enhancing and 57 nonenhancing lesions, were identified among 63 patients. Almost all (99%) of the enhancing lesions were hyperintense to striate nucleus on contrast-enhanced MT images, and most (>87%) showed moderate to marked signal intensity increase from nonenhanced T1-weighted images to contrast-enhanced MT images. Most (>95%) of the nonenhancing lesions showed mild or no increase in relative signal intensity, and most (75%) were iso- or hypointense to striate nucleus on contrast-enhanced MT images. A few nonenhancing lesions (4%-6%), however, showed increase in signal intensity that was indistinguishable from true enhancement without comparison to non-enhanced MT images. CONCLUSION: Nonenhanced MT images should be obtained to assess pathologic enhancement accurately.     

Axial vs sagittal T2-weighted brain MR images in the evaluation of multiple sclerosis

Axial and sagittal proton density and T2-weighted MR images (TR 2,500-3,000 ms, TE 15-22 and 85-90 ms) were performed in 50 patients with multiple sclerosis (MS) on a 1.5 T superconductive system. The number of plaques on the axial and sagittal images in the periventricular white matter, the corpus callosum, the brain stem, the cerebellum, and the basal ganglia were counted separately by two independent observers. A total of 858 lesions (mean 17.40 +/- 21.57) were seen on the axial series and 1,196 (mean 24.32 +/- 26.22) on the sagittal scans. More lesions were visualized on sagittal images in the periventricular region (mean 18.79 +/- 21.69 versus 13.34 +/- 16.45; p less than 0.001) and the corpus callosum (mean 3.00 +/- 2.72 versus 0.57 +/- 1.19; p less than 0.001). In the brain stem more lesions were visualized on the axial images (mean 1.55 +/- 2.55 versus 0.87 +/- 1.20; p less than 0.05). In the cerebellum and basal ganglia, scans in the two planes were equivalent (p greater than 0.5). In three patients lesions were seen on the sagittal series, while the axial scans were normal. Sagittal T2-weighted images appear to demonstrate significantly more MS plaques than transverse images, especially in the periventricular region and the corpus callosum. This is explained by partial volume averaging, by the orientation of some cerebral structures (e.g., corpus callosum) with regard to the section plane, and by the longer diameter of the lesions in the axial plane.     

Improved detection of enhancing and nonenhancing lesions of multiple sclerosis with magnetization transfer.

PURPOSETo determine whether magnetization transfer imaging can improve visibility of contrast enhancement of multiple sclerosis plaques.METHODSFifty-nine enhancing and 63 nonenhancing lesions in 10 patients with multiple sclerosis were evaluated to calculate contrast-to-noise ratios on conventional T1-weighted and T1-weighted magnetization transfer images. The signal intensity of the lesion and the background (white matter) were measured on precontrast T1-weighted and T1-weighted magnetization transfer images (800/20/1 [repetition time/echo time/excitations]) and on postcontrast T1-weighted and T1-weighted magnetization transfer images. Mean contrast-to-noise ratios was calculated for all lesions.RESULTSThe contrast-to-noise ratio was significantly higher for enhancing and nonenhancing lesions on T1-weighted magnetization transfer images than on conventional T1-weighted images. For enhancing lesions, the contrast-to-noise ratio was significantly higher on postcontrast T1-weighted magnetization transfer images, 32 +/- 2 compared with 21 +/- 2 on conventional T1-weighted images. Fifty of the 59 enhancing lesions were seen on both the T1-weighted and the T1-weighted magnetization transfer images. Nine enhancing lesions were seen only on the postcontrast T1-weighted magnetization transfer images. In addition, of 63 nonenhancing lesions seen on proton-density, T2-weighted, and T1-weighted magnetization transfer images, 16 were not seen on the conventional T1-weighted images. Seven of the 63 nonenhancing lesions and 7 of the 59 enhancing lesions had high signal intensity on the precontrast T1-weighted magnetization transfer images suggestive of lipid signal, a finding not seen on the conventional precontrast T1-weighted images.CONCLUSIONMagnetization transfer improves the visibility of enhancing multiple sclerosis lesions, because they have a higher contrast-to-noise ratio than conventional postcontrast T1-weighted images. High signal intensity on both nonenhancing and enhancing lesions noted only on precontrast T1-weighted magnetization transfer suggests a lipid signal was unmasked. If magnetization transfer is used in multiple sclerosis patients, a precontrast magnetization transfer image is necessary.     

T2 relaxation time analysis in patients with multiple sclerosis: correlation with magnetization transfer ratio

The aim of the current study was to perform T2 relaxation time measurements in multiple sclerosis (MS) patients and correlate them with magnetization transfer ratio (MTR) measurements, in order to investigate in more detail the various histopathological changes that occur in lesions and normal-appearing white matter (NAWM). A total number of 291 measurements of MTR and T2 relaxation times were performed in 13 MS patients and 10 age-matched healthy volunteers. Measurements concerned MS plaques (105), NAWM (80), and dirty white matter (DWM; 30), evenly divided between the MS patients, and normal white matter (NWM; 76) in the healthy volunteers. Biexponential T2 relaxation-time analysis was performed, and also possible linearity between MTR and mean T2 relaxation times was evaluated using linear regression analysis in all subgroups. Biexponential relaxation was more pronounced in black-hole lesions (16.6%) and homogeneous enhancing plaques (10%), whereas DWM, NAWM, and mildly hypointense lesions presented biexponential behavior with a lower frequency(6.6, 5, and 3.1%, respectively). Non-enhancing isointense lesions and normal white matter did not reveal any biexponentional behavior. Linear regression analysis between monoexponential T2 relaxation time and MTR measurements demonstrated excellent correlation for DWM(r=–0.78, p<0.0001), very good correlation for black-hole lesions(r=-0.71, p=0.002), good correlation for isointense lesions(r=–0.60, p=0.005), moderate correlation for mildly hypointense lesions(r=–0.34, p=0.007), and non-significant correlation for homogeneous enhancing plaques, NAWM, and NWM. Biexponential T2 relaxation-time behavior is seen in only very few lesions (mainly on plaques with high degree of demyelination and axonal loss). A strong correlation between MTR and monoexponential T2 values was found in regions where either inflammation or demyelination predominates; however, when both pathological conditions coexist, this linear relationship is lost.     

Dirty-appearing white matter in multiple sclerosis: volumetric MR imaging and magnetization transfer ratio histogram analysis

BACKGROUND AND PURPOSE: In contrast to "normal-appearing" white matter (NAWM) in patients with multiple sclerosis (MS), there are subtle, abnormal and diffuse signal intensity changes often seen on T2-weighted MR images, which we have referred to as "dirty-appearing" white matter (DAWM). These areas of DAWM have slightly higher signal intensity than that of NAWM, but lower than that of lesion plaques. Our study was designed to determine the volumetric and magnetization transfer ratio (MTR) features of DAWM in patients with MS. METHODS: Dual-echo fast spin-echo MR imaging and magnetization transfer imaging were performed in 22 patients with relapsing-remitting MS. Slightly hyperintense DAWM areas were manually outlined on the basis of T2-weighted imaging findings. The volume and MTR of DAWM were calculated and compared with the volume and MTR of NAWM and T2 lesion plaques. RESULTS: The average volume of DAWM (18.3 mL) was greater than the average volume of T2 lesion plaques (11.0 mL, P =.04), and the mean MTR in DAWM (38.7%) differed significantly (P <.0001) from that in NAWM (40.7%) and plaques (33.3%). There was a modest negative correlation between either mean MTR (r = -0.60; P =.003) of DAWM or peak height (r = -0.50; P =.02) of DAWM with T2 lesion load. Neither DAWM volume nor total T2 abnormality (DAWM + plaques) volume correlates with the Expanded Disability Status Scale. CONCLUSION: The results of this study indicate that MTR is able to differentiate DAWM from lesion plaques and NAWM and that DAWM might be a different pathologic process of the disease. The notion and quantification of these subtle imaging findings of DAWM areas may improve our understanding of certain stages of disease progression and disease burden in patients with relapsing-remitting MS.     

Guidelines for using quantitative magnetization transfer magnetic resonance imaging for monitoring treatment of multiple sclerosis

Quantitative evaluation of brain magnetic resonance imaging (MRI) scans is now an accepted part of the trial of new putative treatments for multiple sclerosis (MS). However, conventional MRI is not pathologically specific, and it does not reveal the details of the pathological processes that underlie the progression of the disease. Magnetization transfer (MT) imaging is a relatively new quantitative technique that appears to offer some pathological specificity, and can be used to monitor the changes over time in both individual lesions and the central nervous system as a whole. This paper considers the case for incorporating MT imaging into new clinical trials, so that the utility of MT for monitoring the modification of MS progression by treatment can be assessed. Specific guidelines for implementing MT imaging as part of a large multicenter clinical trial are given, and practical considerations when planning such a trial are detailed. It is anticipated that MT imaging will be incorporated into many new trials in the near future.