Magnetization Transfer Contrast Imaging Research Articles

Magnetization transfer contrast imaging reveals amyloid pathology in Alzheimer's disease transgenic mice

The presence of amyloid plaques in the brain is one of the pathological hallmarks of Alzheimer's disease, which might already be present in the early stage of the disease. Therefore it is important to track amyloid plaques as early as possible. In this paper, we report magnetization transfer contrast magnetic resonance imaging (MTC MRI) as a novel approach to detect amyloid plaques in vivo. Two mice models, APP/PS1 and BRI, developing amyloid pathology were investigated with MTC MRI, T2 relaxation measurements and immunohistochemistry (IHC). MT-ratios of several brain regions were compared to T2-values and correlated with quantitative IHC, revealing amyloid load and gliosis in different brain regions. APP/PS1 mice develop large compact plaques, resembling late stage Alzheimer's disease, while rather small and diffuse plaques are deposited in BRI mice, reflecting early stage of Alzheimer's disease. We found significantly higher MT-ratio's in the brain of APP/PS1 mice as compared to their controls and similar trends in BRI mice. A region based MT-ratio and IHC analysis and correlations between MT-ratios and quantitative IHC indicate amyloid plaques as the main substrate for altered MT-ratios in transgenic animals. We additionally demonstrated the improved sensitivity of MTC MRI to amyloid pathology as compared to traditional T2 relaxation measurements. Our results suggest that MTC MRI reveals extensive, and potentially even early amyloid pathology. Further unraveling the MT-effect of each pathological feature during each stage of AD might indicate MTC MRI as a useful diagnostic technique.

Use of Magnetization Transfer Contrast MRI to Detect Early Molecular Pathology in Alzheimer's Disease

The purpose of this study was to determine if magnetization transfer contrast (MTC) imaging could be used to detect early macromolecular accumulation in a mouse model of early Alzheimer's disease. We obtained MTC images at 9.4 T at three different age points in the Tg2576 mouse model of Alzheimer's disease. The Tg2576 mouse exhibits increased amyloid beta deposition that eventually progresses into amyloid beta plaque formation, increased hyper-phosphorylated tau but does not exhibit neurodegeneration. Our results show an increase in the MTC signal that predates plaque formation and reported learning and memory deficits in the Tg2576 mouse. This increase in the MTC signal was reversed in a model of antioxidant therapy. MTC magnetic resonance imaging can be used to detect early macromolecular changes in the Tg2576 mouse model of Alzheimer's disease. The source of the MTC contrast is likely complex and warrants further investigation in additional preclinical models that represent early and late stage Alzheimer's disease pathologies.

Corticospinal Tract MR Signal-Intensity Pseudonormalization on Magnetization Transfer Contrast Imaging: A Potential Pitfall in the Interpretation of the Advanced Compromise of Upper Motor Neurons in Amyotrophic Lateral Sclerosis

We read the article by Carrara et al,[1][1] entitled “A Distinct MR Imaging Phenotype in Amyotrophic Lateral Sclerosis: Correlation between T1 Magnetization Transfer Contrast Hyperintensity along the Corticospinal Tract and Diffusion Tensor Imaging Analysis,” with great interest. The possible

Magnetization Transfer in Human Achilles Tendon Assessed by a 3D Ultrashort Echo Time Sequence: Quantitative Examinations in Healthy Volunteers at 3T

Magnetization transfer contrast (MTC) imaging provides insight into interactions between free and bounded water. Newly developed ultrashort echo time (UTE) sequences implemented on whole-body magnetic resonance (MR) scanners allow MTC imaging in tissues with extremely fast signal decay such as tendons. The aim of this study was to develop a technique for the quantification of the MT effect in healthy Achilles tendons in-vivo at 3 Tesla. 16 normal tendons of volunteers with no history of tendinopathy were examined using a 3D-UTE sequence with a rectangular on-resonant excitation pulse and a Fermi-shaped off-resonant MT preparation pulse. The frequency of the MT pulse was varied from 1 to 5 kHz. MT effects were calculated in terms of the MT ratio (MTR) between measurements without and with MT preparation. Direct saturation effects of MT preparation on the signal intensity were evaluated using numerical simulation of Bloch equations. One patient with tendinopathy was examined to exemplarily show changes of MTR under pathologic conditions. Calculation of MTR data was feasible in all examined tendons and showed a decrease from 0.53 ± 0.05 to 0.25 ± 0.03 (1 kHz to 5 kHz) for healthy volunteers. Evaluation of variation with gender and dominance of ankle revealed no significant differences (p > 0.05). In contrast, the patient with confirmed tendinopathy showed MTR values between 0.36 (1 kHz) and 0.19 (5 kHz). MT effects in human Achilles tendons can be reliably assessed in-vivo using a 3D UTE sequence at 3 T. All healthy tendons showed similar MTR values (coefficient of variation 10.0 ± 1.2 %). The examined patient showed a clearly different MT effect revealing a changed microstructure in the case of tendinopathy.

Clinical Significance of Magnetization Transfer Contrast Imaging for Edematous Changes in Masticatory Muscle

To evaluate inflammatory changes in masticatory muscles by magnetization transfer contrast (MTC) imaging. Gradient-recalled echo (GRE) and MTC-GRE images of relaxed masticatory muscles in 28 healthy volunteers were obtained before and after exercise. At the same time, muscle stiffness and pain in the masseter muscles were also measured. Magnetization transfer ratios (MTRs) of the muscles were calculated from the GRE and MTC-GRE images. The MTRs of the masticatory muscles in 50 patients with temporomandibular disorder were compared with those in the volunteers. Immediately after the exercise, the MTRs of the masseter muscles significantly decreased (P < 0.05), whereas muscle stiffness and pain increased in the healthy volunteers. In patients with masseter muscle pain, the MTRs of the masseter muscles were significantly lower than in the healthy volunteers (P < 0.05). Magnetization transfer contrast imaging strongly reflects the masticatory muscle edematous changes, possibly leading to masseter muscle pain.

Magnetization transfer contrast imaging in bovine and human cortical bone applying an ultrashort echo time sequence at 3 Tesla

Magnetization transfer (MT) contrast imaging reveals interactions between free water molecules and macromolecules in a variety of tissues. The introduction of ultrashort echo time (UTE) sequences to clinical whole-body MR scanners expands the possibility of MT imaging to tissues with extremely fast signal decay such as cortical bone. The aim of this study was to investigate the MT effect of bovine cortical bone in vitro on a 3 Tesla whole-body MR unit. A 3D-UTE sequence with a rectangular-shaped on-resonant excitation pulse and a Gaussian-shaped off-resonant saturation pulse for MT preparation was applied. The flip angle and off-resonance frequency of the MT pulse was systematically varied. Measurements on various samples of bovine cortical bone, agar gel, aqueous manganese chloride solutions, and solid polymeric materials (polyurethane) were performed, followed by preliminary applications on human tibial bone in vivo. Direct on-resonant saturation effects of the MT prepulses were calculated numerically by means of Bloch's equations. Corrected for direct saturation effects dry and fresh bovine cortical bone showed "true" MTR values of 0.26 and 0.21, respectively. In vivo data were obtained from three healthy subjects and showed MTR values of 0.30 +/- 0.08. In vivo studies into MT of cortical bone might have the potential to give new insights in musculoskeletal pathologies.

Systematic Variation of Off-Resonance Prepulses for Clinical Magnetization Transfer Contrast Imaging at 0.2, 1.5, and 3.0 Tesla

The aim of the presented study was to evaluate pulsed magnetization transfer contrast (MTC) effects using saturation pulses of variable off-resonance frequency and radio frequency (RF) amplitude for a variety of tissue types (white and gray matter, liver, kidney, spleen, muscle, and articular cartilage) in human subjects at field strengths of 0.2, 1.5, and 3.0 Tesla. MTC imaging studies of the head, knee, and abdomen were performed using an adapted multiple MTC (mMTC) module in 3 healthy volunteers for all field strengths. This mMTC pulse module applies a variable Gaussian shaped magnetization transfer (MT) saturation pulse in a proton-density weighted RF-spoiled gradient echo sequence. It allows for both a flexible MT pulse design and performance of consecutive measurements with variation of amplitude and off-resonance frequency, whereas keeping other MT pulse parameters unchanged. Magnetization transfer signal ratio (MTR) maps were calculated on a pixel-by-pixel basis. Additional mMTC imaging measurements were performed using an agar-water phantom. For assessment of undesired direct saturation effects of the MT pulse on the water pool, numerical simulations based on Bloch's equations were performed and analyzed. The results indicate that MTR values for given MT pulses (pulse shape, off-resonance frequency and flip angle) are larger at higher magnetic field strengths. For white matter, gray matter, cartilage, and muscle, an increase of 10% to 30% was found at 3.0 T when compared with 1.5 T. Low magnetic field strength of 0.2 T led to MTR values of one third to half the values at 1.5 T. MTR values for abdominal tissues were partly lower at 3.0 T compared with 1.5 T, which might be related to reduced B1 field strengths at 3.0 T due to dielectric effects. The increased MT effect at a higher field strength can partly compensate the specific absorption rate related problems in MTC applications. It is shown that for flip angles of 700 degrees to 900 degrees and offset frequencies of 1000 Hz to 1500 Hz, high quality MTR maps could be obtained at an acceptable level of direct saturation for all field strengths. Furthermore, if the better signal-to-noise ratio at higher magnetic fields is taken into account, quality of MTR maps of the head and the knee at 3.0 T was clearly improved compared with lower fields under optimized and comparable conditions.

Whole‐body magnetization transfer contrast imaging

To demonstrate the feasibility of whole-body magnetization transfer (MT) contrast imaging. Whole-body MT imaging was performed on eight healthy volunteers and five patients (mean age=40.5+/-17.8 years) with diagnoses of dermatomyositis (N=1), B-symptoms with suspicion of paraneoplastic disease (N=1), metastatic malignant melanoma (N=1), and multiple sclerosis (MS) (N=2). Measurements were carried out on a 1.5-Tesla whole-body MR scanner capable of parallel signal reception. A three-dimensional (3D) gradient-echo sequence (TR=17 msec, TE=4.8 msec, flip angle=10 degrees) was applied in combination with a Gaussian off-resonance MT preparation pulse acting at an off-resonance of 1.500 Hz with a 500 degrees effective flip angle. Whole-body images were constructed from five different body regions. In all subjects, whole-body MT contrast images were obtained within less than 20 minutes of measuring time. The images showed sufficient diagnostic image quality to assess the patients' pathologies. The MT ratios (MTRs, in percent units) for the volunteers were as follows: white matter (WM) 51.1+/-1.0, gray matter (GM) 42.2+/-1.3, skeletal muscle (mean value of four muscle groups) 50.3+/-2.1, liver 39.4+/-3.2, spleen 31.8+/-2.6, renal cortex 30.4+/-1.9, and renal medulla 25.6+/-1.3. The MTRs for the pathologies were as follows: skeletal muscle in dermatomyositis approximately 30, metastases in malignant melanoma 30.7-36.0, uterus myoma 49.3, and MS lesions 30-40. Our preliminary data indicate that MT contrast in whole-body MRI is feasible, and may be useful for rapid whole-body assessment of diseases that exhibit high contrast in MT imaging, such as MS and muscular disorders.

Fast 3D coronary artery contrast-enhanced magnetic resonance angiography with magnetization transfer contrast, fat suppression and parallel imaging as applied on an anthropomorphic moving heart phantom

A magnetic resonance sequence for high-resolution imaging of coronary arteries in a very short acquisition time is presented. The technique is based on fast low-angle shot and uses fat saturation and magnetization transfer contrast prepulses to improve image contrast. GeneRalized Autocalibrating Partially Parallel Acquisitions (GRAPPA) is implemented to shorten acquisition time. The sequence was tested on a moving anthropomorphic silicone heart phantom where the coronary arteries were filled with a gadolinium contrast agent solution, and imaging was performed at varying heart rates using GRAPPA. The clinical relevance of the phantom was validated by comparing the myocardial relaxation times of the phantom's homogeneous silicone cardiac wall to those of humans. Signal-to-noise ratio and contrast-to-noise ratio were higher when parallel imaging was used, possibly benefiting from the acquisition of one partition per heartbeat. Another advantage of parallel imaging for visualizing the coronary arteries is that the entire heart can be imaged within a few breath-holds.

Bilateral neurostimulation systems used for deep brain stimulation: in vitro study of MRI-related heating at 1.5 T and implications for clinical imaging of the brain

Deep brain stimulation (DBS) is used increasingly in the field of movement disorders. The implanted electrodes create not only a prior risk to patient safety during MRI, but also a unique opportunity in the collection of functional MRI data conditioned by direct neural stimulation. We evaluated MRI-related heating for bilateral neurostimulation systems used for DBS with an emphasis on assessing clinically relevant imaging parameters. Magnetic resonance imaging was performed using transmit body radiofrequency (RF) coil and receive-only head RF coil at various specific absorption rates (SARs) of RF power. In vitro testing was performed using a gel-filled phantom with temperatures recorded at the electrode tips. Each DBS electrode was positioned with a single extension loop around each pulse generator and a single loop at the "head" end of the phantom. Various pulse sequences were used for MRI including fast spin-echo, echo-planar imaging, magnetization transfer contrast and gradient-echo techniques. The MRI sequences had calculated whole-body averaged SARs and local head SARs ranging from 0.1 to 1.6 W/kg and 0.1 to 3.2 W/kg, respectively. Temperature elevations of less than 1.0 degrees C were found with the fast spin-echo, magnetization transfer contrast, gradient-echo and echo-planar clinical imaging sequences. Using the highest SAR levels, whole-body averaged, 1.6 W/kg, local exposed-body, 3.2 W/kg, and local head, 2.9 W/kg, the temperature increase was 2.1 degrees C. These results showed that temperature elevations associated with clinical sequences were within an acceptable physiologically safe range for the MR conditions used in this evaluation, especially for the use of relatively low SAR levels. Notably, these findings are highly specific to the neurostimulation systems, device positioning technique, MR system and imaging conditions used in this investigation.

Magnetization Transfer Contrast(MTC)効果における基礎的検討 : 自作ファントムによるMTパルスの最適化

Magnetization transfer contrast (MTC) was evaluated by changing the off-set frequency and pulse intensity of MTC with the spoiled gradient echo (SPGR) sequence (T2*-weighted image) using an experimental phantom that included olive oil, protein, fiber, collagen, and pure water. The intensity of pure water reached a constant level just above the off-set frequency (1200 Hz) regardless of MT pulse power. The contrast-to-noise ratio (CNR) in each of the phantom materials was maximal at the MT pulse power of 2500 degrees (equivalent flip angle). The CNR and image noise obtained by body coil were inferior to those obtained with an extremity coil. In clinical application, the MTC effect on chondrosarcoma was higher (MT ratio, ROI-1:0.448, ROI-2:0.382) than those of other cases in this study. Since the image contrast was improved between the malignant fibrous histiocytoma (MFH, MT ratio, ROI-1:0.282, ROI-2:0.289) and peripheral tissues, extraskeletal extension could be observed more easily than without MTC imaging. In conclusion, the effects of MTC might be in providing useful information, in presuming composed tissues, differential diagnoses, and extent to the surrounding structures because of changing the image contrast to surrounding tissues corresponding to the rate of included bound water.

Magnetization transfer contrast imaging in Niemann pick type C mouse liver.

To investigate livers of mice afflicted with Niemann Pick type C (NP-C) disease using magnetization transfer contrast (MTC) imaging and to test the hypothesis that the MT ratio reproducibly changes during disease progression. NP-C is a heritable defect of lipid metabolism that results in the accumulation of unesterified cholesterol and gangliosides in virtually all cells. Symptoms predominate in brain and liver, which have high endogenous rates of lipid turnover. It is fatal to children, usually early in the second decade of life. Previous work has shown that the efficiency of magnetization transfer (MT) can be affected by cholesterol and collagen in tissues. The MT ratio (MTR) was calculated and compared during growth and therapy of diseased and control mice. Significant differences in the MTR were observed between livers of diseased and control mice. These ratios were consistent with collagen deposition associated with fibrosis, and not the accumulation of unesterified cholesterol in this organ. These results indicate that MTC imaging may have clinical potential for monitoring progression and therapy in NP-C disease.

MR Imaging of Epidermoids at the Cerebellopontine Angle

The most common location of intracranial epidermoid is the cerebellopontine angle (CPA). The present study compared the visibility of epidermoid at the CPA in various pulse sequences. Seven patients with epidermoid at the CPA underwent conventional MR imaging (T(1)-, T(2)- and proton density-weighted imaging) as well as diffusion-weighted echo-planar imaging. Fast fluid-attenuated inversion recovery (FLAIR) sequences, magnetization transfer contrast (MTC) sequences, and MR cisternography were employed for selected patients. The signal intensity of the lesions relative to cerebrospinal fluid (CSF), the degree of lesion demarcation and the displacement of surrounding structures were evaluated. Proton density-weighted imaging depicted the lesions as hyper-intense to CSF with clearer delineation than T(1)- and T(2)-weighted imaging. Diffusion-weighted imaging depicted all lesions as strongly hyper-intense relative to CSF and brain tissue. FLAIR sequences depicted the lesions with mixed signal intensities but with poor-to-medium demarcation. MTC imaging increased delineation of the lesions to some degree. MR cisternography depicted the lesions as hypo-intense to CSF and clearly showed the anatomical relation to neighboring nerves and vessels. We concluded that diffusion-weighted imaging could specifically reveal an epidermoid at the CPA as a strongly hyper-intense lesion, and that MR cisternography is mandatory for preoperative planning.

MR Imaging of Articular Cartilage: Comparison of Magnetization Transfer Contrast and Fat - Suppression inMultiplanar and 3D Gradient-Echo, Spin-Echo, Turbo Spin-Echo Techniques

Purpose : The purpose of this study was to evaluate the effects of magnetization transfer contrast(MTC) andfat-suppression(FS) in variable spin-echo and gradient-echo sequences for articular cartilage imaging and todetermine the optimal pulse sequences. Materials and Methods : Using variable 7-pulse sequences, the knees of 15pigs were imaged Axial images were obtained using proton density and T2-weighted spin-echo (PDWSE and T2WSE),turbo spin-echo (TSE), multiplanar gradient-echo (MPGR), and 3D steady-state gradient-echo (3DGRE) sequences, andthe same pulse sequences were then repeated using MTC. Also T1-weighted spin-echo(T1WSE) and 3D spoiledgradient-echo(3DSPGR) images of knees were also acquired, and the procedure was repeated using FS. For each knee,a total of 14 axial images were acquired, and using a 6-band scoring system, the visibility of and thevisibilities of the the articular cartilage was analyzed. The visual effect of MTC and FS was scored using a4-band scale. For each image, the signal intensities of articular cartilage, subchondral bone, muscles, and salinewere measured, and signal-to-noise ratios(SNR) and contrast-to-noise ratios(CNR) were also calculated. Results :Visibility of the cartilage was best when 3DSPGR and T1WSE sequences were used. MTC imaging increased the negativecontrast between cartilage and saline, but FS imaging provided more positive contrast. CNR between cartilage andsaline was highest when using TSE with FS(-3 5 1 . 1 ±15.3), though CNR between cartilage and bone then fell to-1 4 . 7 ±10.8. In MTC imaging using MPGR showed the greatest increase of negative contrast between cartilage andsaline(CNR change=-74.7); the next highest was when 3DGRE was used(CNR change=-34.3). CNR between cartilage andbone was highest with MPGR(161.9 ±17.7), but with MTC, the greatest CNR decrease(-81.8) was observed. Thegreatest CNR increase between cartilage and bone was noted in T1WSE with FS. In all scans, FS provided acartilage-only positive contrast image, though the absolute value of CNR was lower than that of MTC imaging.Conclusion : The most prominent effects of MTC and FS were seen in MPGR and T1WSE, respectively, though forcartilage, optimal high signal intensity and contrast can be achieved using 3DGRE with MTC, and 3DSPGR with FS.

Magnetization transfer contrast (MTC) and long repetition time spin-echo MR imaging in multiple sclerosis

Purpose: To study whether application of magnetization transfer contrast (MTC) improves visibility and detection of multiple sclerosis (MS) lesions on long repetition time (TR) conventional spin-echo (CSE) or fast spin-echo (FSE) magnetic resonance (MR) imaging. Material and methods: In 20 patients and 5 controls, MR images were obtained using long repetition time CSE and FSE sequences with and without MTC. Signal-to-noise ratios of normal appearing white matter (NAWM) and selected lesions, and contrast-to-noise ratios between lesions and NAWM, were calculated. Lesions were counted and total lesion volume was measured in a blinded fashion for each sequence. Results: In controls, MT effect in white matter (16.3% vs. 12.2%) was higher for CSE than for FSE ( p < 0.01). Application of MTC to either CSE or FSE resulted in a significantly lower decrease in signal intensity of NAWM in patients compared to white matter in controls ( p < 0.01). Furthermore, in patients signal intensity of lesions was less decreased than signal intensity of NAWM ( p < 0.01). Compared to sequences without MTC, contrast-to-noise ratios were significantly higher on both CSE (10.9%) and FSE (6.3%) when MTC was applied ( p < 0.01). Despite better visibility, the number of lesions detected on either sequences did not increase when MTC was applied. For CSE with MTC, we found an almost equal number of lesions and for FSE with MTC, we found even less lesions ( p < 0.01). Total lesion volume did not change significantly when MTC was applied. Conclusion: Although contrast between lesions and NAWM improved when magnetization transfer contrast was applied, this did not increase detection of MS lesions on either CSE or FSE MR imaging.

Magnetization Transfer Imaging of Rat Brain under Non-steady-state Conditions. Contrast Prediction Using a Binary Spin–Bath Model and a Super-Lorentzian Lineshape

Magnetization transfer contrast imaging using turbo spin echo and continuous wave off-resonance irradiation was carried out on rat brainin vivoat 4.7 T. By systematically varying the off-resonance irradiation power and the offset-frequency, the signal intensities obtained under steady-state for both transverse and longitudinal magnetization were successfully analyzed with a simple binary spin–bath model taking into account a free water compartment and a pool of protons with restricted motions bearing a super-Lorentzian lineshape. Due to important RF power deposition, such experimental conditions are not practical for routine imaging on humans. An extension of the model was derived to describe the system for shorter off-resonance pulse duration, i.e., when the longitudinal magnetization of the free protons has not reached a steady-state. Data sets obtained for three regions of interest, namely thecorpus callosum,the basal ganglia, and the temporal lobe, were correctly interpreted for off-resonance pulse durations varying from 0.3 to 3 s. The parameter sets obtained from the calculations made it possible to predict the contrast between the different regions as a function of the pulse power, the offset frequency, and pulse duration. Such an approach could be extended to contrast prediction for human brain at 1.5 T.

Magnetization transfer imaging in vivo of the rat brain at 4.7 T: interpretation using a binary spin-bath model with a superLorentzian lineshape.

Proton magnetization transfer contrast (MTC) imaging, using continuous wave off-resonance irradiation, was performed on the rat brain in vivo at 4.7 Tesla. The observed MTC was studied in three different brain regions: the corpus callosum, the basal ganglia, and the temporal lobe. By systematically varying the offset frequency and the amplitude of the RF irradiation, the observed signal intensities for each region of interest were modeled using a system including free water and a pool of protons with restricted motions (R. M. Henkelman, X. Huang, Q. Xiang, G. J. Stanisz, SD Swanson, M. J. Bronskill, Magn. Res. Med. 29, 759 (1993)). Most of the relaxation parameters of both proton pools remained fairly constant for the three regions of interest, with a T2 value of about 9 micros for the immobilized protons, whereas the rate of exchange increased significantly from the temporal lobe to the corpus callosum. The optimal acquisition parameters for the improved MTC under steady-state saturation were found to be 2-10 kHz offset frequency and 500-800 Hz RF irradiation amplitude. Conversely, an irradiation amplitude of 3 kHz at an offset frequency of 12 kHz is required to minimize the direct effect of off-resonance irradiation. Such an approach could be extended to human brain imaging with the aim of characterizing tissue-specific disease.

Sensitivity of contrast enhanced MRI in multiple sclerosis. Effects of gadolinium dose, magnetization transfer contrast and delayed imaging

Although clinical end points remain the definitive measure of therapeutic efficacy in multiple sclerosis, more sensitive markers of disease activity are required to screen potential disease-modifying agents. The use of gadolinium contrast-media in MRI studies increases both the reliability and sensitivity of detecting active lesions in multiple sclerosis. We studied three potential methods for further improving sensitivity; the use of 0.3 mmol/kg (triple dose) gadolinium-diethylenetriaminepenta-acetic acid (Gd-DTPA), magnetization transfer (MT) contrast imaging and the introduction of a delay between contrast-medium injection and imaging. Fifty patients were studied (seven with benign, 14 with relapsing-remitting, 10 with secondary progressive, 16 with primary progressive and three with transitional multiple sclerosis). Imaging was performed on two occasions, 24-72 h apart, with triple- and single-dose Gd-DTPA. Pairs of contrast-enhanced T 1-weighted studies, with and without MT, were obtained at three different times, i.e. within early (0-20 min), short-delay (20-40 min) and long-delay (40-60 min) time-windows. Nineteen patients did not have the full complement of studies. Seven patients suffered minor self-limiting adverse events possibly related to triple-dose Gd-DTPA. Overall, triple-dose Gd-DTPA resulted in a 75% increase in the number of enhancing lesions detected compared with the single dose (P < 0.002). The use of MT or delay alone did not significantly increase the sensitivity of either single- or triple-dose studies. The combination of MT and short delay increased the number of enhancing lesions detected with single-dose Gd-DTPA by 47% (P < 0.05) and with triple-dose Gd-DTPA by 27% (P < 0.01). Detection was not significantly further improved by a long delay. The most sensitive modality was MT imaging with a long delay following triple-dose Gd-DTPA, resulting in the detection of 126% more enhancing lesions than in standard single-dose imaging (P < 0.05). This applies to all subgroups except for primary progressive multiple sclerosis, in which none of these methods alone or in combination improved the sensitivity. We conclude that for relapsing-remitting and secondary progressive multiple sclerosis, the combination of triple-dose Gd-DTPA and delayed MT imaging more than doubles the sensitivity to contrast-enhancing lesions.

The value of new MRI techniques in adrenoleukodystrophy.

To evaluate the significance of new techniques in MRI examinations of the brain in children with X-linked adrenoleukodystrophy (ALD). Five patients aged between 2 and 15 years with childhood ALD were examined with MRI. Following conventional spin-echo (CSE) sequence, a fast spin-echo (FSE) sequence with T2 contrast was performed in four patients, an FSE turbo-inversion-recovery (TIR) sequence in two, magnetization transfer contrast (MTC) imaging in two, and localized proton spectroscopy (MRS) in four patients. FSE compared favorably with CSE with a time saving of 70%. On TIR images the contrast between normal and demyelinated white matter was greater than on CSE and FSE images. Calculated MTC values revealed a severe MTC loss within the demyelinated regions and a moderate reduction in the border zones. In this way, calculation of MTC might be useful to differentiate between edematous changes and areas of irreversible demyelination. MRS revealed a reduction in N-acetylaspartate and an elevation in choline (Cho). The degree of MRS changes paralleled the severity of demyelination. A Cho elevation may precede visible demyelination on T2-weighted images. T2-weighted FSE sequences can replace CSE without any disadvantages and with effective time saving. The indication for MTC imaging and MRS in children with ALD is not yet finally defined. These new techniques may reveal the earliest signs of cerebral involvement or of disease progression, a matter of great importance in selecting the optimal therapeutic approach.

A chronological evaluation of experimental brain infarct by diffusion-mapping and magnetization transfer contrast imaging.

There is a complex system of evolving physiochemical processes in the ischemic brain. The evaluation of this chain of processes is a major challenge of recent stroke studies. Two magnetic resonance imaging techniques: diffusion-weighted (DW) and magnetization transfer contrast (MTC) imaging were introduced in experimental studies and were shown to have sensitivity for different stages of brain infarct. We used a reproducible middle cerebral artery (MCA) occlusion model in rat to examine infarcts of different time courses. Magnetic resonance T2-weighted (T2). DW, and MTC imaging were performed 3 h, 1 d, 3 d, 5 d, 2 w, 3 w, and 4 w after MCA occlusion. Haematoxylin/eosin (HE) stained sections, which revealed sub regions within infarct lesions, were compared to T2, DW, diffusion-mapping and MTC-mapping images. On DW images 3 hours post occlusion lesions were detected as an area with high signal intensity, while T2 imaging does not raise significant contrast of the lesion at this early stage. Three sub regions of the lesion having different ADCs, are discernible on diffusion-mapping images from 1 day to 7 days. The decrease of MTC effect was measured within the infarct lesion from core to marginal zone, from 7 days to 4 weeks. Diffusion-mapping imaging may help to examine brain infarction from 3 hours to 5 days. MTC imaging recognizes infarcts 7 days after the onset. Following this stage, MTC-mapping images may provide a quantitative method to assess infarct size.