Magnetisation transfer ratios of contrast-enhancing and nonenhancing lesions in multiple sclerosis

Magnetisation transfer (MT) is a recently introduced technique for assessing the water content of tissues in vivo and its relationship to macromolecules or membranes. It has been suggested that MT could provide indirect evidence of the characteristics of multiple sclerosis (MS) lesions (oedema, demyelination, or gliosis). Our aims were to characterise brain MS lesions and to compare the magnetisation transfer ratio (MTR) values of lesions with different patterns of contrast enhancement. In patients with MS we measured the MTR of 65 gadolinium-enhancing and 292 nonenhancing lesions. Using the equation published by Dousset et al. we studied 29 patients with clinically definite MS and 10 healthy controls. Lesions had significantly lower MT than the normal-appearing white matter of the patients or the normal white matter of healthy controls. There was no difference in the MTR of enhancing and nonenhancing lesions. Enhancement was homogeneous in 45 and ring-like in 20 lesions; MTR values were lower in the latter. These findings are presumably related to the differences in pathological features of enhancing (different amounts of proteins and inflammatory cells, oedema and demyelination) and nonenhancing (gliosis, demyelination and axonal loss) lesions.     

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.     

Brain MR post-gadolinium contrast in multiple sclerosis: the role of magnetization transfer and image subtraction in detecting more enhancing lesions

Our purpose was to evaluate the role of magnetization transfer and image subtraction in detecting more enhancing lesions in brain MR imaging of patients with multiple sclerosis (MS). Thirty-one MS patients underwent MR imaging of the brain with T1-weighted spin echo sequences without and with magnetization transfer (MT) using a 1.5 T imager. Both sequences were acquired before and after intravenous injection of a paramagnetic contrast agent. Subtraction images in T1-weighted sequences were obtained by subtracting the pre-contrast images from the post-contrast ones. A significant difference was found between the numbers of enhanced areas in post-gadolinium T1-weighted images without and with MT (p=0.020). The post-gadolinium T1-weighted images with MT allowed the detection of an increased (13) number of enhancing lesions compared with post-gadolinium T1-weighted images without MT. A significant difference was also found between the numbers of enhanced areas in post-gadolinium T1-weighted images without MT and subtraction images without MT (p=0.020). The subtraction images without MT allowed the detection of an increased (10) number of enhancing lesions compared with post-gadolinium T1-weighted images without MT. Magnetization transfer contrast and subtraction techniques appear to be the simplest and least time-consuming applications to improve the conspicuity and detection of contrast-enhancing lesions in patients with MS.     

Quantitative magnetization transfer and myelin water imaging of the evolution of acute multiple sclerosis lesions

Quantitative magnetization transfer imaging provides in vivo estimates of liquid and semisolid constituents of tissue, while estimates of the liquid subpopulations, including myelin water, can be obtained from multicomponent T₂ analysis. Both methods have been suggested to provide improved myelin specificity compared to conventional MRI. The goal of this study was to investigate the sensitivity of each technique to the progression of acute, gadolinium‐enhancing regions of multiple sclerosis. Magnetization transfer and T₂ relaxometry data were acquired longitudinally over the course of 1 year in five relapsing‐remitting multiple sclerosis patients and in five healthy controls. Parametric maps were analyzed in enhancing lesions and normal‐appearing white matter regions. Quantitative magnetization transfer parameters in lesions were most abnormal at the time of enhancement and followed a pattern of recovery over subsequent months. Lesion myelin water fraction was abnormal but did not show a significant trend over time. Quantitative magnetization transfer was able to track the degree and timing of the partial recovery in enhancing multiple sclerosis lesions in a small group of patients, while the recovery was not detected in myelin water estimates, possibly due to their large variability. Our data suggest the recovery is characterized by quick resolution of inflammation and a slower remyelination process. Magn Reson Med, 2010. © 2010 Wiley‐Liss, Inc.     

Experimental allergic encephalomyelitis and multiple sclerosis: lesion characterization with magnetization transfer imaging.

Magnetization transfer imaging (MTI) was initially performed in normal guinea pigs and human volunteers. A magnetization transfer ratio (MTR) was calculated in the normal white matter and was found to be 42%-44%, with less than 2.5% variation, which indicates the high reproducibility of the measurement. MTI was then applied to an animal model of white matter disease, acute experimental allergic encephalomyelitis (EAE). In this model of EAE, pathologically proved lesions were edematous with essentially no demyelination. MTRs decreased slightly but significantly (5%-8%) compared with the MTRs of the same tissue region measured before the onset of the lesion [corrected]. Fifteen patients with multiple sclerosis (MS) also underwent MTI. In the 15 patients with MS, all lesions (209 plaques) had a significantly decreased MTR (average, 26%). The authors believe that demyelination produced the lower MTR, and, thus, lesions varied in transfer ratio on the basis of the extent of myelin loss. In patients with MS, particularly those with chronic and/or progressive MS, the MTR of the normal-appearing white matter was significantly decreased. The data suggest that calculated MTR obtained with in vivo MTI may enable differentiation of edema from demyelination, and that MTI can demonstrate white matter abnormalities that cannot be seen with standard spin-echo or gradient-echo magnetic resonance imaging.     

Improved visualization of breast lesions with gadolinium-enhanced magnetization transfer MR imaging

A pulse sequence with magnetization transfer as the main contrast mechanism (MT-FLASH) was developed for improved imaging of breast lesions that requires neither fat suppression nor postprocessing. After optimization of the sequence in phantom and volunteer studies, a clinical pilot study with 14 patients was performed. In carcinomas the relative signal increase after Gd-DTPA administration was on average 34% in MT-FLASH images compared with 169% in conventional T₁ weighted (T1W) three-dimensional FLASH images. In MT-FLASH images, all lesions demonstrated a signal intensity higher than that of fat; in T1W images, all lesions have a lower signal intensity. The average postcontrast carcinoma-to-fat contrast-to-noise ratios were +11.6 and ?14.2, respectively. The conspicutty of 12 of 13 carcinomas was improved in postcontrast MT-FLASH images compared with postcontrast T1w images. Thus, MT-FLASH imaging enables excellent visualization of Gd-DTPA-enhancing breast lesions.     

Characterization of multiple sclerosis plaques with T1-weighted MR and quantitative magnetization transfer.

PURPOSETo investigate the relationship between the appearance of multiple sclerosis lesions identified on unenhanced T1-weighted images and their corresponding magnetization transfer ratios.METHODSA total of 119 white matter lesions seen on T2-weighted images in 17 patients with multiple sclerosis were evaluated. Axial T1-weighted images were used to classify the lesions as isointense to white matter (10 lesions), hypointense to white matter but hyperintense to gray matter (44 lesions), hypointense to gray matter (59 lesions), and relatively isointense to cerebrospinal fluid (6 lesions). The magnetization transfer ratio of each lesion was calculated, and an average magnetization transfer ratio for each subcategory was determined.RESULTSThe magnetization transfer ratio values became progressively lower with increasing hypointensity of lesions on T1-weighted images. The average magnetization transfer ratio for lesions isointense to white matter, hypointense to white matter but hyperintense to gray matter, hypointense to gray matter, and relatively isointense to cerebrospinal fluid was 34.90 +/- 2.67 mean +/- SD), 30.93 +/- 3.57, 27.27 +/- 3.56, and 23.62 +/- 2.83, respectively. All groups were significantly different from each other.CONCLUSIONLesions isointense to white matter exhibited higher magnetization transfer ratio values than lesions that were hypointense. These findings are consistent with relative preservation of the myelin structure in the former, perhaps indicating that these lesions are predominantly inflammatory (edematous) in nature. The proportionately lower magnetization transfer ratio values of lesions that appear progressively more hypointense on T1-weighted images may reflect varying degrees of demyelination, with increasing lesion hypointensity corresponding to more breakdown in the macromolecular structure. These results suggest that T1-weighted images may be useful in characterizing the underlying pathologic substrate in multiple sclerosis plaques.     

Quantitative magnetization transfer imaging in postmortem multiple sclerosis brain

PURPOSE: To investigate the relationship of myelin content, axonal density, and gliosis with the fraction of macromolecular protons (fB) and T2 relaxation of the macromolecular pool (T2B) acquired using quantitative magnetization transfer (qMT) MRI in postmortem brains of subjects with multiple sclerosis (MS). MATERIALS AND METHODS: fB and T2B were acquired in unfixed postmortem brain slices of 20 subjects with MS. The myelin content, axonal count, and severity of gliosis were all quantified histologically. t-Tests and multiple regression were used for analysis. RESULTS: MR indices obtained in unfixed postmortem MS brains were consistent with in vivo values reported in the literature. A significant correlation was detected between Tr(myelin) (inversely proportional to myelin content) and 1) fB (r = -0.80, P < 0.001) and 2) axonal count (r = -0.79, P < 0.001). fB differed between 1) normal-appearing white matter (NAWM) and remyelinated WM lesions (rWMLs) (mean: fB 6.9 [SD 2] vs. 4.0 [1.8], P = 0.01), and 2) rWMLs and demyelinated WMLs (mean: 4.2 [2.2] vs. 2.5 [1.3], P = 0.016). No association was detected between T2B and any of the histological measures. CONCLUSION: fB in MS WM is dependent on myelin content and may be a tool to monitor patients with this condition.     

Computer-assisted quantitation of enhancing lesions in multiple sclerosis: correlation with clinical classification.

PURPOSETo study the utility of a computer-assisted method of quantitating enhancing multiple sclerosis (MS) lesions and to correlate this quantitation with the type and duration of disease.METHODSForty untreated patients with MS were studied. The patients had been classified clinically as having either relapsing-remitting (n = 27) or chronic-progressive (n = 13) disease. Postcontrast contiguous 3-mm-thick MR images of the brain were obtained for up to 3 years. The computer program selected potential lesion sites automatically on the basis of the theory of "fuzzy connectedness," which was incorporated into 3DVIEWNIX software. True lesions were selected from these previously detected potential lesions by means of yes/no responses to the program query. The number of enhancing lesions and the enhancing lesions volume were subsequently computed.RESULTSThe enhancing lesion volume in patients with relapsing-remitting disease was statistically significantly higher than that of patients with chronic-progressive disease. There was a strong positive correlation between the number of enhancing lesions and the enhancing lesion volume. No significant correlation was noted between the change in score on the expanded disability status scale (EDSS) and the change in the number of enhancing lesions, or between the change in EDSS score and the change in enhancing lesion volume. A negative correlation was found between enhancing lesion volume and duration of disease, and between the number of enhancing lesions and duration of disease in the patients who had enhancing lesions.CONCLUSIONSOur data suggest that enhancing lesion volume reflects differences in the classification of clinical MS and in the disease activity over time. Computer-assisted quantitation of enhancing lesion volume is a robust, practical, and objective measure of MS activity.     

Computed tomography: regression of periventricular enhancing lesions in multiple sclerosis.

A patient with two periventricular enhancing lesions on computed tomography subsequently demonstrated clearing of these abnormalities without treatment and a clinical course compatible with multiple sclerosis. CT scans obtained in disease processes associated with acute demyelination and alteration of the blood-brain barrier can show enhancing lesions. These lesions can initially be confused with primary or secondary neoplasms, enhancing infarcts or arteriovenous malformation. The differential diagnosis of enhancing lesions without significant mass effect should initially include the acute phase of multiple sclerosis and other demyelinating processes.     

Quantitative magnetization transfer mapping of bound protons in multiple sclerosis

Quantitative analysis of magnetization transfer images has the potential to allow a more thorough characterization of the protons, both bound and free, in a tissue by extracting a number of parameters relating to the NMR properties of the protons and their local environment. This work develops previously presented techniques to produce estimates of parameters such as the bound proton fraction, f, and the transverse relaxation time of the bound pool, T(2B), for the whole brain in a clinically acceptable imaging time. This is achieved by limiting the number of data collected (typically to 10); to collect 28 5-mm slices with a reconstructed resolution of 0.94 x 0.94 mm. The protocol takes 82 sec per data point. The fitting technique is assessed against previous work and for fitting failures. Maps and analysis are presented from a group of seven controls and 20 multiple sclerosis patients. The maps show that the parameters are sensitive to tissue-specific differences and can detect pathological change within lesions. Statistically significant differences in parameters such as T(2B) and f are seen between normal-appearing white matter, multiple sclerosis lesions, and control white matter. Whole-brain histograms of these parameters are also presented, showing differences between patients and controls.     

Characterization of white matter lesions in multiple sclerosis and traumatic brain injury as revealed by magnetization transfer contour plots.

BACKGROUND AND PURPOSE: Magnetization transfer imaging provides information about the structural integrity of macromolecular substances, such as myelin. Our objective was to use this imaging technique and contour plotting to characterize and to define the extent of white matter lesions in multiple sclerosis and traumatic brain injury. METHODS: Magnetization transfer imaging was performed of 30 multiple sclerosis plaques and 10 traumatic white matter lesions. Magnetization transfer ratios (MTRs) were calculated for the lesions, for the normal- or abnormal-appearing surrounding white matter, and for remote normal-appearing white matter. MTR contour plots were constructed about these lesions. RESULTS: The contour plot appearance of MS plaques differed from that of traumatic white matter lesions. There was a gradual increase in MTR values at points at increasing distances from the center of the MS plaques; this was true for those lesions with and without surrounding T2 signal abnormality (halos). In contrast, there was an abrupt transition in MTR values between traumatic lesions and normal-appearing surrounding white matter. Additionally, the size of the MTR abnormality exceeded the size of the T2 signal abnormality for the MS plaques. CONCLUSION: MTR contour plots permit characterization and border definition of white matter lesions. Analysis of the contour plots suggests that MS is a centrifugal process with the lowest MTR within the center of the lesion. In contrast, traumatic white matter injuries are discrete lesions with abrupt transitions between the abnormal lesion and normal brain.     

Texture analysis of magnetization transfer maps from patients with clinically isolated syndrome and multiple sclerosis

Purpose

To investigate the behavior of texture parameters derived from the gray level co‐occurrence matrix from gray matter (GM) and white matter (WM) (with lesions removed) segments of magnetization transfer ratio maps from controls and patients.

Materials and Methods

Magnetization transfer ratio maps from 23 controls and patients with either a clinically isolated syndrome (CIS) (38 patients) or clinically definite multiple sclerosis (MS) (35) were scanned and texture parameters extracted. The texture parameters were compared between the groups and correlated with clinical measures of disability in the MS patients to investigate any association with disease severity.

Results

No significant differences were found between the texture parameters from controls and CIS patients; however, several parameters differ between MS patients and the two other groups, particularly in the GM, but also in the WM. The expanded disability status score and timed walk test correlate with GM texture measures, while the Paced Auditory Serial Addition Test 3 score, a cognitive measure, correlates with WM texture. Texture abnormalities were seen in MS WM and GM, indicating tissue damage beyond classical WM lesions, the abnormalities being more evident in GM.

Conclusion

The findings highlight potential for texture analysis measures in classifying central nervous system demyelinating diseases that warrants further investigation. J. Magn. Reson. Imaging 2009;30:506–513. © 2009 Wiley‐Liss, Inc.     

Brain magnetic resonance with magnetization transfer in multiple sclerosis. Lesion hyperintensity before and after intravenous gadolinium administration

PURPOSE: The possibility of detecting contrast agent extravasation (i.e., active hemorrhage) with dynamic conventional Computed Tomography (CT) in patients with abdominal trauma has already been reported in small series. We report our experience in the demonstration of contrast material extravasation using helical CT; we also investigate the diagnostic and clinical value of this finding. MATERIAL AND METHODS: January 1997 to July 1998, we examined 41 consecutive patients with upper abdominal trauma. Twelve patients (29%) had contrast material extravasation. The examinations were performed with a helical unit and volumetric acquisitions (thickness 8-10 mm, pitch 1, reconstruction interval 5-8 mm). The intravenous contrast medium (350 mgI/mL, 130-140 mL) was administered with rapid infusion (2-2.5 mL/s, 40-50 s acquisition delay from bolus starting) and using a power injector. We reviewed the CT studies and clinical records of these 12 patients. Contrast agent extravasation was considered present when this finding, not recognizable on plain scans, showed equal attenuation to or higher attenuation than the vessels within the same level. Moreover we assessed leak site, CT appearance, the direct visualization of the involved vessel, the evidence of other abdominal or extra-abdominal injuries, the CT signs of hypovolemic shock, clinical and surgical data. For comparison, we finally evaluated 50 examinations performed with a conventional CT scanner in subjects with abdominal trauma. RESULTS: Active hemorrhage involved the abdominal wall in 1 case (intercostal artery), the solid organs in 4 (splenic in 2, hepatic in 1, of the middle hepatic vein in 1), the peritoneal cavity in 3 (splenic, midcolic, and gastroduodenal artery in 1 each), the retroperitoneum in 4 (renal pedicle in 2, renal parenchyma in 1, lumbar artery in 1). In all cases the site of contrast extravasation corresponded at surgery to the site of active bleeding. The pattern was localized in 10 cases and diffuse in 2. The involved vessel could be identified in 5 cases while in the other ones the origin could be inferred from the leakage site. Associated injuries of upper abdominal organs were seen in 11 of 12 patients and extra-abdominal trauma in 6. In 4 cases there were CT features of hypovolemia. One patient died during transport to the operating room and another after surgery, while all the others survived. Contrast extravasation was identified in 9 (18%) of the patients examined with a conventional CT unit. CONCLUSIONS: Active contrast material extravasation can be recognized with conventional CT scanners, though it has been considered a rare finding. Helical CT seems to increase the detection rate and especially to boost the radiologist's confidence in this diagnosis. Though active bleeding is identified in severely-injured subjects requiring urgent intervention and may be associated with findings of hypovolemic shock, it should not be considered itself as a negative prognostic factor. Contrast extravasation is due to ongoing hemorrhage and its detection is critical for urgent treatment. Accurate anatomical location permits to choose surgical management or transcatheter embolization and thus decreases time consumption for precise bleeding site identification.     

Global volumetric estimation of disease burden in multiple sclerosis based on magnetization transfer imaging.

We report a semiautomated postprocessing method based on magnetization transfer MR imaging that can quantify the extent of global disease in patients with multiple sclerosis. The technique combines segmentation and quantitative analysis of imaging data reflecting the structural integrity of white matter. Applications of this technique may include assessment of disease progress and of the efficacy of experimental therapeutic intervention. The height of the histogram peak corresponding to white matter was found to be lowered in patients with multiple sclerosis and the overall distribution of magnetization transfer ratios was shifted to lower values.     

Correlation of spectroscopy and magnetization transfer imaging in the evaluation of demyelinating lesions and normal appearing white matter in multiple sclerosis

Magnetization transfer imaging (MT) and localized proton spectroscopy (¹H-MRS) were utilized in the evaluation of lesioins (high signal abnormalities on T₂-weighted images) and normal-appearing white matter (NAWM) in multiple sclerosis (MI). Eleven patients with a clinical diagnosis of MS were independently evaluated with both ¹H-MRS and MT. The magnetization transfer ratio (MTR) of lesions was compared with the relative concentration of Kacetyl-aspartate (NAA) and a composite peak at 2.1 to 2.6 ppm termed “marker peaks”. The MTR of white matter lesions in the MS patients was markedly decreased (6–34%; normal ≈?42%), and correlated well with increase in the marker peaks region (0.94–3.89). There was no correlation between the relative concentration of NAA and MTR. Increased resonance peaks in the 2.1 to 2.6 ppm range and marked decreases in MTR may be a relatively specific indicators of demyelination.     

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.