Mean Magnetization Transfer Ratio Research Articles

Regional Specificity of Magnetization Transfer Imaging in Multiple Sclerosis

The goal of this study was to develop and validate a method for generation of regional magnetization transfer ratio (MTR). We also studied the topography of MTR changes in multiple sclerosis (MS) and in normal controls (NC), and preliminarily examined the clinical usefulness of this method. We examined 45 patients with MS (relapsing remitting [RR] = 28 and secondary progressive[SP] = 17] and 19 NC. Mean disease duration was 14.3 years and median Expanded Disability Status Scale was 3.0. Regions of the brain were determined using semiautomated brain region extraction (SABRE). Twenty-six regional masks were automatically applied to MTR maps that were further split into gray matter (GM) and white matter (WM)compartments. Mean MTR from 12 SABRE regions differed significantly between MS patients and NC. For WM, all regional mean MTRs differed significantly between RR, SP, and NC participants(P < .001). In regression analysis, only 3 regions remained significantly different when corrected for total T2-LV. The regression model predicting disability selected GM mean MTR of the right medial inferior frontal region (P = .031). The study results showed that this regional MTR approach is reproducible, reliable and clinically relevant. MTI changes occur selectively in specific sub-regions.

Localized grey matter damage in early primary progressive multiple sclerosis contributes to disability

Disability in primary progressive multiple sclerosis (PPMS) has been correlated with damage to the normal appearing brain tissues. Magnetization transfer ratio (MTR) and volume changes indicate that much of this damage occurs in the normal appearing grey matter, but the clinical significance of this remains uncertain. We aimed to localize these changes to distinct grey matter regions, and investigate the clinical impact of the MTR changes. 46 patients with early PPMS and 23 controls underwent MT and high-resolution T1-weighted imaging. Patients were scored on the Expanded Disability Status Scale (EDSS), Multiple Sclerosis Functional Composite and subtests (Nine-Hole Peg Test, Timed Walk Test, Paced Auditory Serial Addition Test [PASAT]). Grey matter volume and MTR were compared between patients and controls, adjusting for age. Mean MTR for significant regions within the motor network and in areas relevant to PASAT performance were correlated with appropriate clinical scores, adjusting for grey matter volume. Patients showed reduced MTR and atrophy in the right pre- and left post-central gyri, right middle frontal gyrus, left insula, and thalamus bilaterally. Reduced MTR without significant atrophy occurred in the left pre-central gyrus, left superior frontal gyri, bilateral superior temporal gyri, right insula and visual cortex. Higher EDSS correlated with lower MTR in the right primary motor cortex (BA 4). In conclusion, localized grey matter damage occurs in early PPMS, and MTR change is more widespread than atrophy. Damage demonstrated by reduced MTR is clinically eloquent.

Magnetization transfer MRI for quantitative assessment of intestinal fibrosis in Crohnʼs disease

To develop a non-invasive method for detecting and quantifying intestinal fibrosis in patients with Crohn's disease using magnetization transfer (MT) magnetic resonance imaging (MRI). MT-MRI is more specific than traditional MRI for detecting tissue fibrosis by differentiating between free tissue water and water closely associated with macromolecules such as collagen. We hypothesize that changes in the MT signal profile can be used to differentiate and quantitatively characterize intestinal fibrosis, and will be more sensitive and specific for fibrosis than traditional MRIT1 and T2 relaxation times. Intestinal fibrosis was experimentally induced in Lewis strain rats. During laparotomy peptidoglycan-polysaccharide (PG-PS) was injected subserosally into the intestinal wall of the cecum, ileum, and distal Peyer's patches of four rats. Five control animals were similarly injected with human serum albumin (HSA). The PG-PS injected animals developed chronic intestinal inflammation, granulomas, and intense fibrosis 21 days after injection. Ex vivo intestinal tissue samples were scanned in a Varian Inova 2.0 T, 31 cm clear bore system equipped with Acustar S-180 actively shielded gradients and an MR probe. For magnetization transfer, a series of RF pulses were applied from -100 Hz to + 100 kHz off-resonance at three different RF power levels. In vivo MT-MRI images of a whole rat abdomen were also obtained. After undergoing MT-MRI scanning, intestinal histopathology determined the extent of tissue fibrosis. The standard MR imaging parameters, T1 and T2 relaxation times, as well as the MT data were recorded for both PG-PS and HSA samples. There was no difference between the T1 and T2 relaxation times. The MT data were analyzed and reduced into factors indicating the percent solid matter and overall tissue rigidity. The MT ratio (MTR) = 100*(1 -Msat/Mo) where Msat represents MT signal at 10 kHz off-resonance, and Mo represents MT signal at 100 kHz off-resonance. The mean MTR from PG-PS rats was 46.27 (SD 4.14), and control rats was 38.07 (SD 4.76). This demonstrated a statistically significant difference (p = 0.03) between fibrotic and non-fibrotic tissue. Histopathology confirmed the presence of fibrosis in the PG-PS rats, and lack of fibrosis in the control rats. (1) As expected, the data demonstrate that standard T1 and T2 relaxation times were not appreciably different. This confirms that traditional MRI is not sufficiently sensitive to detect intestinal fibrosis. (2) The MT data collected from rats with experimental Crohn's were statistically significantly different than control rats without fibrosis. This supports our hypothesis that MT-MRI can be used to distinguish intestinal fibrosis from non-fibrotic tissue. Furthermore, the MT profile provides a quantification of tissue fibrosis which will allow the clinician to follow disease progression. This technique has the significant advantage over currently available imaging modalities without exposing the subject to ionizing radiation.

A longitudinal conventional and magnetization transfer magnetic resonance imaging study of optic neuritis

Eleven consecutive patients with a first episode of acute optic neuritis were evaluated, using conventional and magnetization transfer (MT) magnetic resonance imaging (MRI), in order to assess the temporal evolution of optic nerve (ON) damage and to investigate the correlation of ON damage with visual outcome and electrophysiological parameters. Patients underwent neuro-ophthalmological, neurological, electrophysiological, and MRI assessments at baseline and after three and 12 months. ON volumes were measured on coronal T1–weighted images using a local thresholding segmentation technique. MT ratio (MTR) from the ON was derived from gradient echo images. No significant volume difference was detected between affected and healthy ON, both at baseline and follow-up. At baseline, mean MTR values were significantly higher in affected ON than in healthy ON (P = 0.001), whereas at months 3 and 12, the mean MTR values were significantly reduced in the affected ON (P = 0.02 and 0.003, respectively). Mean MTR of the affected ON, corrected for healthy ON values, progressively decreased over time (P = 0.04 at month 3 and P = 0.0012 at month 12). On the contrary, MTR values of healthy ON remained stable. No correlations were found between MTR measures and clinical or electrophysiological data. This study shows the presence of subtle pathological changes, possibly due to residual demyelination and subsequent additional demyelination and impaired remyelination, in the ON of patients with a first episode of optic neuritis. In the early phase of optic neuritis, MT MRI is more sensitive than atrophy measurements in detecting disease-related changes. Multiple Sclerosis 2007; 13: 265–268. http://msj.sagepub.com

Non-arteritic anterior ischaemic optic neuropathy: evaluation of the brain and optic pathway by conventional MRI and magnetisation transfer imaging

The purpose of the study was to examine the brain and the visual pathway of patients with non-arteritic anterior ischaemic optic neuropathy (NAION) by using conventional MRI (cMRI) and volumetric magnetisation transfer imaging (MTI). Thirty NAION patients, aged 67.5 +/- 8.14 years, and 28 age- and gender-matched controls were studied. MTI was used to measure the magnetisation transfer ratio (MTR) of the chiasm and for MTR histograms of the brain. The presence of areas of white matter hyperintensity (WMH) was evaluated on fluid-attenuated inversion recovery (FLAIR) images. Area of the optic nerves (ONs) and volume of the chiasm were assessed, as were coronal short-tau inversion recovery (STIR) and MTI images, respectively. More areas of WMH were observed in patients (total 419; mean 14.4; SD 19) than in controls (total 127; mean 4.7; SD 5.7), P < 0.001. Area (in square millimetres) of the affected ONs, volume(in cubic millimetres) and MTR (in percent) of the chiasm (10.7 +/- 4.6), (75.8 +/- 20.2), (56.4 +/- 6.5), respectively, were lower in patients than in controls (13.6 +/- 4.3), (158.2 +/- 75.3) (62.1 +/- 6.2), respectively, P < 0.05. Mean MTR of brain histograms was lower in patients (53.0 +/- 8.0) than in controls (58.0 +/- 5.6), P < 0.05. NAION is characterised by decreased ON and chiasmatic size. The low MTR of the chiasm and brain associated with increased areas of WMH may be suggestive of demyelination and axonal damage due to generalised cerebral vascular disease.

A simple correction for B1 field errors in magnetization transfer ratio measurements

B1 errors are a problem in magnetization transfer ratio (MTR) measurements because the MTR value is dependent on the amplitude of the magnetization transfer (MT) pulse. B1 errors can arise from radiofrequency (RF) nonuniformity (caused by the RF coil, or skin effect and dielectric resonance in the subject's head) and also from inaccurate setting of the transmitter output when compensating for varying amounts of loading of the RF coil. B1 errors, and hence MTR errors, may be up to 5-10%, a large source of error in quantitative MR measurements. Radiofrequency nonuniformity may cause MTR histograms to be broadened. The dependence of MTR on B1 was modeled using binary spin bath theory, with a continuous wave (CW) approximation. For B1 reductions of up to 20%, normalized plots for different brain tissue types could be approximated by a single line, indicating that a systematic correction could be applied to MTR measurements with a known B1 error, regardless of tissue type. On a 1.5-T scanner with a birdcage coil, MTR was measured in 18 tissue types in five controls. The MT pulse amplitude was reduced in steps from its nominal value by up to 20%. Averaging data over all controls and tissue types resulted in a line fitting mtr(normalized)=0.812b(1normalized)+0.193, where mtr(normalized) is the normalized value of MTR (relative to its value at the nominal B1) and b(1normalized) is the normalized value of B1 (relative to its nominal value). For a 20% reduction in MT pulse amplitude (i.e., b(1normalized)=0.80), the mean MTR value for the 18 tissue types was 7.0 percent units (pu) below the correct value. After correction using the single equation above for all tissue types, all MTR values were within 1.5 pu of their correct value [root mean square (rms) error=0.7 pu]. Magnetization transfer ratio values tended to be slightly overcorrected because the simple linear correction scheme is only an approximation to the true MTR dependence on B1. A B1 field mapping technique was implemented, based on the double angle method (DAM), with fast spin-echo (FSE) readout, and TR=15 s; this took a total of 6 min of imaging time. This was used to quantify B(1) errors and correct MTR maps and histograms. However, the cerebrospinal fluid (CSF) T1 is very long (approximately 4.2 s); thus, to achieve complete longitudinal relaxation (a requirement of the DAM B1 mapping method), an increase in TR and, hence, acquisition time would be required. In general, however, we are not interested in calculating the B1 in the CSF, although it is important that the B1 is determined in partial volume voxels around the CSF. Using our birdcage head coil, whole-brain B1 histograms were found to have full-width half maximums (FWHMs) ranging from just 6.8% to 11.5% of the nominal B1 value. The FSE DAM B1 field mapping technique was shown to be robust, although a longer TR time may be desirable to ensure complete elimination of CSF partial volume errors. The procedure can be applied on any scanner where the Euro-MT sequence is available, or alternatively, where the amplitude of B1 or of the MT pulse can be manually reduced in order to perform this type of "calibration" experiment for the particular MTR sequence used. The MTR is known to be highly dependent on the parameters of the sequence used, in particular, the MT pulse shape, flip angle, duration, and offset frequency, and the repetition time TR' between successive MT pulses. Therefore, correction schemes will differ for different MTR sequences, and new data sets would be required to calculate these different correction schemes.

Increasing normal–appearing grey and white matter magnetisation transfer ratio abnormality in early relapsing–remitting multiple sclerosis

Abnormalities within normal-appearing grey and white matter (NAGM and NAWM) occur early in the clinical course of multiple sclerosis (MS) and can be detected in-vivo using the magnetisation transfer ratio (MTR). To better characterize the rates of change in both tissues and to ascertain when such changes begin, we serially studied a cohort of minimally disabled, early relapsing-remitting MS patients, using NAGM and NAWM MTR histograms. Twenty-three patients with clinically definite early relapsing-remitting MS (mean disease duration at baseline 1.9 years), and 19 healthy controls were studied. A magnetisation transfer imaging sequence was acquired yearly for two years. Twenty-one patients and 10 controls completed followup. NAWM and NAGM MTR histograms were derived and mean MTR calculated. A hierarchical regression analysis, adjusting for brain parenchymal fraction,was used to assess MTR change over time. MS NAWM and NAGM MTR were significantly reduced in comparison with controls at baseline and, in patients, both measures decreased further during follow-up: (-0.10 pu/year, p=0.001 and -0.18 pu/year, p<0.001 respectively). The rate of MTR decrease was significantly greater in NAGM than NAWM (p=0.004). Under the assumption that such changes are linear, backward extrapolation of the observed rates of change suggested that NAWM abnormality began before symptom onset. We conclude that increasing MTR abnormalities in NAWM and NAGM are observed early in the course of relapsing-remitting MS. It is now important to investigate whether these measures are predictive of future disability, and consequently, whether MTR could be used as a surrogate marker in therapeutic trials.

Magnetization transfer ratio in neuro-Beh�et disease

The aim of this study was to determine the contribution of magnetization transfer ratios (MTRs) in detecting disease in normal-appearing brain regions of patients with neuro-Behçet (NB) disease. Thirty-two patients with NB disease were assessed. Fifteen healthy volunteers were examined as the control group. Magnetic resonance (MR) imaging of the head was performed without and with magnetization transfer (MT) contrast. Signal intensity measurements were obtained from ten anatomical regions (centrum semiovale, corona radiata, internal capsule, forceps major, forceps minor, thalamus, substantia nigra pars compacta, substantia nigra pars grisea, inferior pons and middle cerebellar peduncle) in both groups. Also measured in the NB group were parenchymal lesions in the brain stem, basal ganglia and cerebral deep white matter. MTR was calculated for each measurement. Statistical analysis was performed with Mann-Whitney U and independent t-tests with computer-based SPSS 11.0 for Windows software. A P value below 0.05 was considered statistically significant. The mean MTR of the parenchymal lesions in the NB group was lower than the mean MTR of the normal-appearing parenchyma in both the NB patients and the normal group. For the normal-appearing parenchyma the mean MTR in the NB group was higher than that for the controls for all regions except the corona radiata; however, the difference was statistically significant only for the thalamus. The MRI-visible parenchymal involvement of Behçet's disease causes a decrease in MTR. For the normal-appearing brain, although lacking statistical significance for the most regions studied, the tendency for higher MTR in NB patients compared with controls may offer an insight into the pathophysiology of Behçet's disease.

Selective gray matter damage in neuropsychiatric lupus.

Damage of brain parenchyma in patients with primary diffuse neuropsychiatric systemic lupus erythematosus (NPSLE) has been indicated by magnetization transfer imaging (MTI). However, the location of MTI abnormalities is unknown. This study was undertaken to assess the distribution of MTI abnormalities over gray matter (GM) and white matter (WM) in SLE patients with a history of NP symptoms without explanatory magnetic resonance imaging (MRI) evidence of focal disease. MTI was performed in 24 female SLE patients with a history of diffuse NP symptoms and 24 healthy female controls. Magnetization transfer ratio (MTR) maps were calculated for GM and WM separately, and GM and WM MTR histograms were generated. Univariate and multivariate analyses with age as an additional covariate were performed on the histogram parameters peak location (PL), peak height (PH), and mean MTR. Compared with controls, significantly reduced PH (mean +/- SD 136 +/- 22 arbitrary units versus 151 +/- 13 arbitrary units) and mean MTR (33.3 +/- 1.0 percent units versus 33.6 +/- 0.5 percent units) were found in the GM of NPSLE patients (P = 0.002 and P = 0.033, respectively, in multivariate analyses). No significant differences were observed for WM MTR parameters. This is the first study to demonstrate, using MTI, that in SLE patients with a history of NP symptoms and without explanatory focal abnormalities on MRI, the GM is particularly affected. These findings support the hypothesis that neuronal injury may underlie central nervous system manifestations in NPSLE.

Cervical spinal cord MTR histogram analysis in multiple sclerosis using a 3D acquisition and a B-spline active surface segmentation technique.

The application of a three-dimensional magnetization transfer (MT) sequence and B-spline active surface segmentation method to produce MT histograms of the cervical spinal cord in a pilot study of controls and multiple sclerosis (MS) patients is presented. Subjects' cervical spinal cords were imaged with (a) a volume-acquired inversion-prepared fast spoiled gradient echo sequence and (b) a volume-acquired noninversion-prepared fast spoiled gradient echo MT sequence. The images were segmented using the B spline active surface technique and MT histograms were produced from the MT images. The method was sensitive enough to detect differences between seven MS patients and 10 controls in mean MT ratio (42.4 pu versus 44.0 pu, p = 0.03) and peak location (45.2 versus 46.8, p = 0.03). The spinal cord volumes obtained from the two sequences were associated with each other (parameter estimate 0.972, 95% confidence intervals 0.742, 1.202, p < 0.001).

Evidence for grey matter MTR abnormality in minimally disabled patients with early relapsing-remitting multiple sclerosis

Objectives: To establish whether magnetisation transfer ratio (MTR) histograms are sensitive to change in normal appearing grey matter (NAGM) in early relapsing-remitting multiple sclerosis (RRMS) in the absence of significant...

Serial magnetization transfer imaging in acute optic neuritis

MAGNETIZATION TRANSFER IMAGING (MT) ALLOWS the examination of tissues in more details than conventional MRI. In serial studies of multiple sclerosis lesions, reductions in magnetization transfer ratio (MTR) are thought to be due to demyelination and axonal loss, with later rises due to remyelination. In this study, the authors followed serial changes in MTR in acute optic neuritis in combination with clinical and electrophysiological measurements to determine if the MTR changes over time mirror the picture in multiple sclerosis lesions. They included 29 patients who had acute optic neuritis for a median of 13 days (range 7–24 days) since the onset of visual symptoms. A clinical examination and measurement of visual evoked potentials (VEP) was performed on each patient. Their optic nerves were imaged with a fat-saturated fast spin echo (FSE) sequence and a magnetization transfer sequence. Twenty-one had multiple subsequent examinations over the course of 1 year. In addition, 27 control subjects had their optic nerves imaged up to three times over 1 year. A blinded observer segmented the optic nerves from the MTR maps. Lesions were defined on the acute FSE images and, from the coordinates, the ratio of mean lesion MTR : healthy nerve MTR (lesion ratio) was calculated for each dataset. The time-averaged mean MTR in control optic nerves was 47.7 per cent units (pu). In diseased optic nerves, baseline mean MTR was 47.3 pu, with a mean lesion ratio of 0.98. The diseased optic nerve MTR and lesion ratio declined over time with a nadir at about 240 days at a mean MTR value of 44.2 pu and mean lesion ratio of 0.91. After 1 year the diseased optic nerve mean MTR was 45.1 pu (mean lesion ratio 0.93), although the difference was not significant compared with the nadir value. For each 0.01 increase in time-averaged lesion ratio logMAR visual acuity recovery improved by 0.03 (95% CI, 0.002, 0.08, P = 0.02). Time-averaged VEP central field latency was shorter by 6.1 ms (95% CI 1.5, 10.7, P = 0.012) per 1 pu rise in time-averaged diseased optic nerve MTR. The authors conclude that early fall in diseased optic nerve MTR is consistent with demyelination and Wallerian degeneration of transected axons. The late nadir compared with studies of multiple sclerosis lesions may have been due to slow clearance of myelin debris. Remyelination may have influenced subsequent MTR changes. The observations support using MTR to monitor symptomatic demyelinating lesions.—Valérie Biousse

Disability in multiple sclerosis is related to normal appearing brain tissue MTR histogram abnormalities.

Magnetization transfer ratio (MTR) histogram analysis provides a global measure of disease burden in multiple sclerosis (MS). MTR abnormalities in normal appearing brain tissue (NABT) provide quantitative information on the extent of tissue damage undetected by conventional T2-weighted (T2W) magnetic resonance imaging (MRI). 1) To compare the MTR histograms from NABT across a broad spectrum of relapse onset MS patients, including relapsing-remitting (RR) MS (including newly diagnosed and benign subgroups) and secondary progressive (SP) MS. 2) To determine the relationship between clinical disability and NABT MTR histograms. 2D spin echo magnetization transfer imaging was performed on 70 RRMS and 25 SPMS patients and compared with 63 controls. MTR histograms were acquired for NABT after extracting lesions and cerebrospinal fluid (CSF). T2W images were used to measure the brain parenchymal fraction (BPF) and T2 lesion load. MS patients had a disease duration ranging from 0.5 to 37 years and an Expanded Disability Status Scale (EDSS) score ranging from 0 to 8.5. There was a significant decrease in NABT mean MTR (+/- standard deviation) compared with controls (33.07 pu +/- 1.06 versus 34.26 pu +/- 0.47; P < 0.001) with an effect size of 2.56. The reduction in NABT mean MTR varied among patient groups from 4.9% for SPMS, 3% for all RRMS, 2.7% for early RRMS and 2.5% for benign MS, compared with controls. NABT mean MTR correlated significantly with T2 lesion load (r = -0.82) and BPF (r = 0.58). EDSS score correlated with NABT mean MTR (r = -0.43), BPF (r = -0.33) and with T2 lesion load (r = 0.59). Multivariate analysis using NABT MTR peak height, T2 lesion load and BPF combined only accounted for 38% of the variance in the EDSS (r = 0.62; P < 0.001). Disease duration accounted for an additional 14% of variance in the EDSS (r = 0.72; P < 0.001). There is evidence of diffuse abnormalities in NABT in addition to global brain atrophy in relapse onset MS patients, including those with recently diagnosed RRMS and benign MS. The abnormalities are greatest in patients with the more disabling SPMS. Atrophy, NABT and lesion abnormalities are all partly correlated; the processes marked by these MR measures all contribute to disability in MS, providing complementary information relevant to the complex pathological processes that occur in MS.

Serial magnetization transfer imaging in acute optic neuritis.

In serial studies of multiple sclerosis lesions, reductions in magnetization transfer ratio (MTR) are thought to be due to demyelination and axonal loss, with later rises due to remyelination. This study followed serial changes in MTR in acute optic neuritis in combination with clinical and electrophysiological measurements to determine if the MTR changes over time mirror the picture in multiple sclerosis lesions, further validating MTR as a marker of tissue integrity. Twenty-nine patients were recruited who had acute optic neuritis for a median of 13 days (range 7-24 days) since the onset of visual symptoms. A clinical examination and measurement of visual evoked potentials (VEP) was performed on each patient. Their optic nerves were imaged with a fat-saturated fast spin echo (FSE) sequence and a magnetization transfer sequence. Twenty-one had multiple subsequent examinations over the course of 1 year. In addition, 27 control subjects had their optic nerves imaged up to three times over 1 year. A blinded observer segmented the optic nerves from the MTR maps. Lesions were defined on the acute FSE images and, from the coordinates, the ratio of mean lesion MTR : healthy nerve MTR (lesion ratio) was calculated for each dataset. The time-averaged mean MTR in control optic nerves was 47.7 per cent units (pu). In diseased optic nerves, baseline mean MTR was 47.3 pu, with a mean lesion ratio of 0.98. The diseased optic nerve MTR and lesion ratio declined over time with a nadir at about 240 days at a mean MTR value of 44.2 pu and mean lesion ratio of 0.91. Subsequently, diseased optic nerve MTR appeared to rise; after 1 year the diseased optic nerve mean MTR was 45.1 pu (mean lesion ratio 0.93), although the difference was not significant compared with the nadir value. For each 0.01 increase in time-averaged lesion ratio logMAR visual acuity recovery improved by 0.03 (95% CI, 0.002, 0.08, P = 0.02). Time-averaged VEP central field latency was shorter by 6.1 ms (95% CI 1.5, 10.7, P = 0.012) per 1 pu rise in time-averaged diseased optic nerve MTR. The early fall in diseased optic nerve MTR is consistent with demyelination and Wallerian degeneration of transected axons. The late nadir compared with studies of multiple sclerosis lesions may have been due to slow clearance of myelin debris. Remyelination may have influenced subsequent MTR changes. The observations support using MTR to monitor symptomatic demyelinating lesions.

Biexponential T2 Relaxation Time Analysis of the Brain

To measure T2 relaxation times of normal white and gray matter using a novel CPMG sequence and investigate if any correlation exists between magnetization transfer ratio (MTR) and T2 relaxation-related parameters. Seventeen normal volunteers participated on this study. A single-slice 32-echo sequence was used to calculate the T2 relaxation time of frontal and occipital white matter and cortical gray matter. T2 relaxation analysis included monoexponential and biexponential fitting whereas an F test was used to determine if biexponential fitting was statistically more accurate than monoexponential fitting. Short and long T2 constants were calculated as well as the signal fractions of each pool. MTR calculations were based on a three-dimensional gradient echo (3D FFE) proton density weighted sequence with and without an on-resonance composite prepulse. MTR and T2 relaxation times were calculated and linear regression analysis was applied. Biexponential fitting was more accurate comparing with monoexponential fitting in all WM and GM regions (F > 2.47, P < 0.01). Mean values of short T2 constant for frontal white matter (fWM), occipital white matter (oWM) and gray matter (GM) were 8.10, 9.36, and 22.23 milliseconds, respectively, whereas the mean values of long T2 constant were 85.1, 93.02, and 118.72 milliseconds, respectively. Mean restricted water percentages (RWP)-corresponding to the signal fraction of the protons with short T2-for the fWM, oWM, and GM were 22.01%, 23.36%, and 18.7%. Mean free water percentages (FWP)-corresponding to the signal fraction of the protons with long T2-for the fWM, oWM and GM were 77.99%, 76.64%, and 81.3%. Mean MTR values for fWM, oWM and GM were 68.4%, 68.2%, and 61.3%, respectively. No significant correlation was found in fWM and oWM between MTR and RWP, short and long T2 components while a moderate correlation existed in GM between MTR and RWP (r = 0.57; P = 0.02), MTR and short T2 component (r = -0.69; P = 0.004) and MTR and long T2 component (r = -0.62; P = 0.012). Two proton pools with different T2 decay characteristics can be separated in normal gray and white matter when using a multiecho sequence with short echo spacing. MTR and T2 relaxation times were significantly correlated in gray matter and the combination of both types of measurements may be helpful in studying myelin related disorders.

Magnetization transfer can predict clinical evolution in patients with multiple sclerosis.

The clinical course of multiple sclerosis (MS) is highly variable ranging from benign to aggressive, and is difficult to predict. Since magnetization transfer (MT) imaging can detect focal abnormalities in normal-appearing white matter (NAWM) before the appearance of lesions on conventional MRI, we hypothesized that changes in MT might be able to predict the clinical evolution of MS. We assessed MR data from MS patients who were subsequently followed clinically for 5 years. We computed the mean MT ratio (MTr) in gray matter, in lesions identified on T2-weighted MRI, and in NAWM, as well as in a thick central brain slice for each patient. Patients were divided into stable and worsening groups according to their change in Expanded Disability Status Scale (EDSS) scores over 5 years. We calculated the sensitivity, specificity, predictive value, and odds ratio of the baseline MTr measures in order to assess their prognostic utility. We found significant differences in baseline MTr values in NAWM (p = 0.005) and brain slice (p = 0.03) between clinically stable and worsening MS patients. When these MTr values were compared with changes in EDSS over 5 years, a strong correlation was found between the EDSS changes and MTr values in both NAWM (SRCC = -0.76, p < 0.001) and in the brain slice (SRCC = 0.59, p = 0.01). Baseline NAWM MTr correctly predicted clinical evolution in 15/18 patients (1 false positive and 2 false negatives), yielding a positive predictive value of 77.78 %, a negative predictive value of 88.89 %, and an odds ratio of 28. The relationship between 5-year changes in EDSS and MTr values in T2 weighted MRI lesions was weaker (SRCC = -0.43, p = 0.07). Our data support the notion that the quantification of MTr in the NAWM can predict the clinical evolution of MS. Lower MTr values predict poorer long-term clinical outcome. Abnormalities of MTr values in the NAWM are more relevant to the development of future patient disability than those in the T2-weighted MRI lesions.

Magnetization transfer imaging diagnosis of intracranial tuberculomas.

Tuberculomas (TB) can mimic brain tumors and abscesses. We performed prospective magnetization transfer ratio (MTR) analysis on 60 patients with 52 intracranial TB, 13 pyogenic abscesses and 65 tumors to determine the efficacy of magnetization transfer (MT) imaging in the differential diagnosis of brain tumors and infection. The nonenhancing cores of TB had significantly higher (P=.026) MTR (0.14+/-0.29) than necrotic components of high-grade gliomas (-0.19+/-0.22). The MTR of cores of TB were also higher than those of the cystic areas of low-grade gliomas (-0.53+/-0.32), benign (-0.09+/-0.21) and malignant (-0.07+/-0.25) tumors, and abscesses (-0.03+/-0.13), but the differences were not significant because of the small number of tumors and abscesses. There was also no significant difference between the MTR of abscesses, malignant and benign tumors. Using the criteria of MTR of necrotic center > 0.14 (mean MTR of TB) for diagnosing TB, MTR <-0.03 (mean MTR of abscesses) for diagnosing tumors and MTR between these values for diagnosing abscesses, MTI had diagnostic sensitivity of 68.42%, specificity of 80.49%, and accuracy of 76.67%. The improved diagnostic accuracy of MRI with the addition of MTR analysis from 86.67% to 91.67% and from 85.71% to 87.50% for both radiologists respectively was not significant. MTR analysis helped us to differentiate solitary TB or abscess from low-grade glioma in five patients and to diagnose multiple TB, abscesses, and metastases in four.

Magnetization Transfer Ratio in Mild Cognitive Impairment and Dementia of Alzheimer's Type

Almost half of the elderly subjects that are diagnosed with mild cognitive impairment (MCI) go on to develop dementia of Alzheimer's type (DAT) over a 5-year follow-up. MCI and DAT subjects show regional decreases in the volume of brain structures, which correlate with the cognitive decline among these groups. Volumetric changes are found more consistently in the DAT group than in the MCI group. Since not all MCI subjects demonstrate volumetric decline, we propose that the underlying changes in the structural integrity of the brain, measured using magnetization transfer ratio (MTR), may be used as an additional predictor for abnormal cognitive decline in the elderly. Magnetic resonance (MR) images were obtained in 15 DAT, MCI, and elderly control subjects. Using automatic tissue classification, the brain region of each MR volume was segmented into gray matter and white matter. Mean and standard error of the mean MTR measured within the gray matter was found to be significantly lower in the MCI (30.77 ± 0.29; P = 0.037) and the DAT (29.37 ± 0.41; P = 0.000) group compared to the control group (32.11 ± 0.20). The MTR of white matter was significantly lower only in the DAT group. The gray matter volume was significantly lower (P = 0.000) in the DAT (387.29 ± 26.04 cm3) group compared to controls (532.93 ± 20.53 cm3) and MCI (464.64 ± 16.93 cm3). No significant differences were found in the white matter volume between the three groups. We conclude that changes in MTR are measurable even in the absence of detectable volumetric changes in gray and white matter in the MCI group. Furthermore, MTR changes may present a novel MRI measure for the early diagnosis of dementia of Alzheimer's type.

Magnetisation transfer ratio analysis of normal appearing white matter in patients with familial and sporadic multiple sclerosis

OBJECTIVESTo assess differences in magnetisation transfer ratio (MTR) analysis of normal appearing white matter (NAWM) in patients with familial multiple sclerosis (MS) and those with sporadic MS.METHODS10 patients with familial...

NON-INVASIVE MYOCARDIAL IRON ASSESSMENT IN THALASSAEMIC PATIENTS. T2 relaxometry and magnetization transfer ratio measurements

Purpose: To compare T2 relaxometry and magnetization transfer ratio (MTR) measurements of myocardial tissue in normal volunteers and thalassaemic patients for assessment of the myocardial iron levels. Material and Methods: All examinations were done on a 1 T MR system using a multi-echo spin-echo sequence with 8 echoes for T2 measurements and a gradient echo sequence for MTR measurements. Diastolic cardiac triggering was used in both sequences. Ten patients and 10 normal subjects were included in the study. T2 and MTR measurements were correlated with serum ferritin levels. Results: Regression analysis between T2 and MTR measurements and ferritin demonstrated a reversed linear relationship, (r=−0.932, p<0.05) and (r=−0.824, p<0.05), respectively. Mean T2 relaxation time and mean MTR of the normal subjects (57.95±4.9 ms and 43.70±3.3%) was significantly higher than that of the thalassaemic patients (38.8±6.2 ms and 26.40±6.1%) (p<0.01), respectively. Conclusion: MTR measurements can be used to complement T2 measurements for non-invasive myocardial iron assessment.