Inversion Recovery Ultrashort TE MR Imaging of Myelin is Significantly Correlated with Disability in Patients with Multiple Sclerosis.

BACKGROUND AND PURPOSE: MR imaging has been widely used for the noninvasive evaluation of MS. Although clinical MR imaging sequences are highly effective in showing focal macroscopic tissue abnormalities in the brains of patients with MS, they are not specific to myelin and correlate poorly with disability. We investigated direct imaging of myelin using a 2D adiabatic inversion recovery ultrashort TE sequence to determine its value in assessing disability in MS. MATERIALS AND METHODS: The 2D inversion recovery ultrashort TE sequence was evaluated in 14 healthy volunteers and 31 patients with MS. MPRAGE and T2-FLAIR images were acquired for comparison. Advanced Normalization Tools were used to correlate inversion recovery ultrashort TE, MPRAGE, and T2-FLAIR images with disability assessed by the Expanded Disability Status Scale. RESULTS: Weak correlations were observed between normal-appearing white matter volume (R = -0.03, P = .88), lesion load (R = 0.22, P = .24), and age (R = 0.14, P = .44), and disability. The MPRAGE signal in normal-appearing white matter showed a weak correlation with age (R = -0.10, P = .49) and disability (R = -0.19, P = .31). The T2-FLAIR signal in normal-appearing white matter showed a weak correlation with age (R = 0.01, P = .93) and disability (R = 0.13, P = .49). The inversion recovery ultrashort TE signal was significantly negatively correlated with age (R = -0.38, P = .009) and disability (R = -0.44; P = .01). CONCLUSIONS: Direct imaging of myelin correlates with disability in patients with MS better than indirect imaging of long-T2 water in WM using conventional clinical sequences.

A prospective comparison study of fast T1 weighted fluid attenuation inversion recovery and T1 weighted turbo spin echo sequence at 3 T in degenerative disease of the cervical spine.

OBJECTIVE: This study compared T1 fluid attenuation inversion recovery (FLAIR) and T1 turbo spin echo (TSE) sequences for evaluation of cervical spine degenerative disease at 3 T. METHODS: 72 patients (44 males and 28 females; mean age of 39 years; age range, 27-75 years) with suspected cervical spine degenerative disease were prospectively evaluated. Sagittal images of the spine were obtained using T1 FLAIR and T1 TSE sequences. Two experienced neuroradiologists compared the sequences qualitatively and quantitatively. RESULTS: On qualitative evaluation, cerebrospinal fluid (CSF) nulling and contrast at cord-CSF, disc-CSF and disc-cord interfaces were significantly higher on fast T1 FLAIR images than on T1 TSE images (p < 0.001). No significant difference was seen between the sequences in evaluation of neural foramina and bone-disc interface. On quantitative evaluation, the signal-to-noise ratios of cord and CSF on fast T1 FLAIR images were significantly higher than those on T1 TSE images (p < 0.05). Contrast-to-noise ratios (CNRs) of cord to CSF on T1 FLAIR images were significantly higher than those of T1 TSE images (p < 0.05). CNRs of bone to disc for T1 weighted TSE images were significantly higher than those of T1 FLAIR images (p < 0.05). CONCLUSION: At 3 T, T1 FLAIR imaging is superior to T1 TSE for evaluating cervical spine degenerative disease, owing to higher cord-CSF, disc-cord and disc-CSF contrast. However, intrinsic cord contrast is low on T1 FLAIR images. ADVANCES IN KNOWLEDGE: T1 FLAIR is more promising and sensitive than T1 TSE for evaluation of degenerative spondyloarthropathy and may provide a foundation for development of MR protocols for early detection of degenerative and neoplastic diseases.

Dual inversion recovery ultrashort echo time (DIR-UTE) imaging and quantification of the zone of calcified cartilage (ZCC).

OBJECTIVE: To develop ultrashort echo time (UTE) magnetic resonance imaging (MRI) techniques to image the zone of calcified cartilage (ZCC), and quantify its T2*, T1 and T1ρ. DESIGN: In this feasibility study a dual inversion recovery UTE (DIR-UTE) sequence was developed for high contrast imaging of the ZCC. T2* of the ZCC was measured with DIR-UTE acquisitions at progressively increasing TEs. T1 of the ZCC was measured with saturation recovery UTE acquisitions at progressively increasing saturation recovery times. T1ρ of the ZCC was measured with spin-locking prepared DIR-UTE acquisitions at progressively increasing spin-locking times. RESULTS: The feasibility of the qualitative and quantitative DIR-UTE techniques was demonstrated on phantoms and in six cadaveric patellae using a clinical 3 T scanner. On average the ZCC has a short T2* ranging from 1.0 to 3.3 ms (mean ± standard deviation = 2.0 ± 1.2 ms), a short T1 ranging from 256 to 389 ms (mean ± standard deviation = 305 ± 45 ms), and a short T1ρ ranging from 2.2 to 4.6 ms (mean ± standard deviation = 3.6 ± 1.2 ms). CONCLUSION: UTE MR based techniques have been developed for high resolution imaging of the ZCC and quantitative evaluation of its T2*, T1 and T1ρ relaxation times, providing non-invasive assessment of collagen orientation and proteoglycan content at the ZCC and the bone cartilage interface. These measurements may be useful for non-invasive assessment of the ZCC, including understanding the involvement of this tissue component in osteoarthritis.

Review. The Agfa Mayneord lecture: MRI of short and ultrashort T2 and T2* components of tissues, fluids and materials using clinical systems.

A variety of techniques are now available to directly or indirectly detect signal from tissues, fluids and materials that have short, ultrashort or supershort T2 or T2* components. There are also methods of developing image contrast between tissues and fluids in the short T2 or T2* range that can provide visualisation of anatomy, which has not been previously seen with MRI. Magnetisation transfer methods can now be applied to previously invisible tissues, providing indirect access to supershort T2 components. Particular methods have been developed to target susceptibility effects and quantify them after correcting for anatomical distortion. Specific methods have also been developed to image the effects of magnetic iron oxide particles with positive contrast. Major advances have been made in techniques designed to correct for loss of signal and gross image distortion near metal. These methods are likely to substantially increase the range of application for MRI.

Optimization of iron oxide nanoparticle detection using ultrashort echo time pulse sequences: comparison of T1, T2*, and synergistic T1- T2* contrast mechanisms.

Iron oxide nanoparticles (IONPs) are used in various MRI applications as negative contrast agents. A major challenge is to distinguish regions of signal void due to IONPs from those due to low signal tissues or susceptibility artifacts. To overcome this limitation, several positive contrast strategies have been proposed. Relying on IONP T(1) shortening effects to generate positive contrast is a particularly appealing strategy because it should provide additional specificity when associated with the usual negative contrast from effective transverse relaxation time (T(2)*) effects. In this article, ultrashort echo time imaging is shown to be a powerful technique which can take full advantage of both contrast mechanisms. Methods of comparing T(1) and T(2)* contrast efficiency are described and general rules that allow optimizing IONP detection sensitivity are derived. Contrary to conventional wisdom, optimizing T(1) contrast is often a good strategy for imaging IONPs. Under certain conditions, subtraction of a later echo signal from the ultrashort echo time signal not only improves IONP specificity by providing long T(2)* background suppression but also increases detection sensitivity, as it enables a synergistic combination of usually antagonist T(1) and T(2)* contrasts. In vitro experiments support our theory, and a molecular imaging application is demonstrated using tumor-targeted IONPs in vivo.

Quantifying sclerotic bone metastases with 2D ultra short TE MRI: a feasibility study.

INTRODUCTION: Ultra Short TE MRI allows signal to be detected from tissues with a very short T2.The aims of this study were to optimize a 2D UTE MRI sequence for imaging and quantification of sclerotic bone metastases, establish T2* values of sclerotic components and investigate the feasibility of using the method to assess changes in T2* of sclerotic metastases and their relation to attenuation values in patients on treatment. METHODS: Twenty-two subjects were recruited in 3 cohorts. Cohort 1 was used to optimize the 2-D UTE sequence, cohort 2 was used to establish T2* measurements using a range of TEs and cohort 3 was used to assess T2* changes with treatment response and relate them to changes on electron density as measured by CT Hounsfield Units. RESULTS: Sagittal 2D UTE MRI of the lumbar spine is feasible demonstrating short T2 components in normal volunteers. In patients with bone metastases secondary to prostate carcinoma T2* can be measured and mean T2* of sclerotic metastases measured with TEs of 0.07, 0.27, 0.47 and 0.67 ms was 8.5 ms.T2* shortened by 20.0% in responders and increased by 24.4% in progressors. DISCUSSION: The significant linear relationship between percentage change in T2* as derived from UTE MRI and percentage change in HU from corresponding CT studies is indirect evidence that they are measuring effects of the same process.If the relationship between T2* and electron density holds true in further studies it offers potential for MR guided radiotherapy planning as well as attenuation correction for PET/MRI.

Reduction in cerebral atrophy associated with ethyl-eicosapentaenoic acid treatment in patients with Huntington's disease.

Ultra-pure ethyl-eicosapentaenoic acid (ethyl-EPA), a semi-synthetic ethyl ester of eicosapentaenoic acid, is associated with clinical improvement in motor functioning in Huntington's disease. The aim was to determine the extent to which it might reduce the rate of progress of cerebral atrophy. High-resolution cerebral magnetic resonance imaging scans were acquired at baseline, 6 months and 1 year in up to 34 patients with stage I or II Huntington's disease who took part in a randomized, double-blind, placebo-controlled trial of ethyl-EPA. For each subject and each pair of structural images, the two-timepoint brain volume change was calculated in a double-blind manner. Significant group-level reductions in brain atrophy were observed in the head of the caudate nucleus and the posterior thalamus. These findings show that treatment with ethyl-EPA is associated with significant reduction in brain atrophy, particularly in the caudate and thalamus. No other drug tested in Huntington's disease has shown this effect.

Magnetic resonance imaging of entheses. Part 1.

Entheses are the sites of attachment of a tendon, ligament, or joint capsule to bone. Many features of entheses are adapted to disperse stress and accommodate compressive and shear forces at, or near, boundaries between tendons or ligaments and bone. Of particular interest is calcified and uncalcified fibrocartilage, which has mechanical properties that differ from those of tensile regions of tendons or ligaments, and from bone. Ultrashort echo time (UTE) pulse sequences can identify the specific tissue components of entheses and differentiate cortical bone, calcified fibrocartilage, uncalcified fibrocartilage, and fibrous connective tissue. Magic angle imaging can also differentiate tissues, such as fibrocartilage and tendon, which have different fibre orientations. Understanding the magnetic resonance (MR) appearance of entheses involves consideration of tissue properties, fibre-to-field angle, magic angle effects, pulse sequences, and geometrical factors including fibre-to-section orientation and partial volume effects. New approaches using MR imaging, allow entheses to be visualised with much greater detail than previously possible, and this may help in biomechanical studies, diagnosis of disease including overuse syndromes and spondyloarthropathies, as well as monitoring tissue repair and healing.

Magnetic resonance imaging of entheses. Part 2.

Entheses are the sites of attachment of a tendon, ligament, or joint capsule to bone. In a previous article new options for visualizing entheses and related structures, including ultrashort echo time (UTE) pulse sequences, and magic angle imaging were described. In this article an approach to image interpretation is described together with normal examples using UTE and other pulse sequences with and without magic angle imaging. Examples of images seen in disease are included. The new options for imaging entheses may provide useful options for biomechanical study and recognition of involvement in disease.

Magnetic resonance imaging of facial muscles.

Facial and tongue muscles are commonly involved in patients with neuromuscular disorders. However, these muscles are not as easily accessible for biopsy and pathological examination as limb muscles. We have previously investigated myasthenia gravis patients with MuSK antibodies for facial and tongue muscle atrophy using different magnetic resonance imaging sequences, including ultrashort echo time techniques and image analysis tools that allowed us to obtain quantitative assessments of facial muscles. This imaging study had shown that facial muscle measurement is possible and that useful information can be obtained using a quantitative approach. In this paper we aim to review in detail the methods that we applied to our study, to enable clinicians to study these muscles within the domain of neuromuscular disease, oncological or head and neck specialties. Quantitative assessment of the facial musculature may be of value in improving the understanding of pathological processes occurring within facial muscles in certain neuromuscular disorders.

Artifact simulating subarachnoid and intraventricular hemorrhage on single-shot, fast spin-echo fluid-attenuated inversion recovery images caused by head movement: A trap for the unwary.

BACKGROUND AND PURPOSE: Single-shot, fast spin-echo, fluid attenuated inversion recovery (SS-FSE-FLAIR) images are frequently used to detect disease in the brain and subarachnoid space in confused or uncooperative patients who may move during the examination. In some of these patients, high signal intensity areas are seen on good-quality images in the subarachnoid space and ventricular system in locations not associated with high CSF flow. These artifacts may simulate hemorrhage or leptomeningeal disease. The purpose of this article was to determine the cause of these artifacts, describe ways to recognize them, and find methods to reduce or eliminate them. METHODS: Healthy volunteers were studied on 6 occasions with conventional multisection FSE-FLAIR images and SS-FSE-FLAIR images while at rest and while nodding and rotating their heads at different speeds. In addition, SS-FSE-FLAIR images with different section widths of the initial inverting pulse and a non-section-selective initial inversion pulse were performed with the subjects moving their heads in the same way. The scans of 30 successive patients with acute neurologic syndromes who had been studied with SS-FSE-FLAIR sequences were reviewed for evidence of high signal intensity in the CSF in regions not associated with high CSF flow. RESULTS: Each of the volunteers showed areas of increased signal intensity in CSF at sites apart from those associated with rapid pulsatile CSF flow on SS-FSE-FLAIR images acquired during head motion. The images were otherwise virtually free of motion artifact. The use of a wider initial inversion pulse section and a non-section-selected initial inversion pulse reduced the extent of these artifacts. Nineteen of the 30 patients showed areas of high signal intensity in the CSF in regions not associated with highly pulsatile CSF flow. Six of these patients had negative lumbar punctures for blood and xanthochromia and normal CSF protein levels. CONCLUSION: High signal intensity artifacts may be seen in CSF as a result of head movement on otherwise artifact-free images when imaging uncooperative patients with SS-FSE-FLAIR sequences. These artifacts have a different mechanism and distribution from those caused by CSF pulsation and may simulate subarachnoid and intraventricular hemorrhage. Artifact recognition is aided by signs of patient motion during the examination. The artifacts can be reduced by use of increased section width and non-section-selective initial inversion pulses. Recognition of these artifacts is important, because the circumstances in which the SS-FSE-FLAIR sequence is used and the particular properties of the sequence may conspire to produce a trap for the unwary.

Schizophrenia syndromes associated with changes in ventricle-to-brain ratios: a serial high-resolution three-dimensional magnetic resonance imaging study in first-episode schizophrenia patients using subvoxel registration and semiautomated quantification.

A cohort of patients with first-episode schizophrenia was dichotomised into two age- and sex-matched groups of clinical syndromes, the active and withdrawn, and underwent high-resolution three-dimensional magnetic resonance imaging at baseline and 8 months later. A cohort of age- and sex-matched normal controls was also imaged at the same time intervals. The application of subvoxel registration and semiautomated quantification techniques demonstrated a significantly different outcome in ventricular changes between the two groups of patients. Compared with the controls, the withdrawn patients showed progressive ventricular enlargement, with an increase in ventricle-to-brain volume ratio, whereas the active group showed a reduction in ventricle-to-brain volume ratio, with a change opposite in sign and smaller in magnitude. These findings lend further support for the aetiological validity of this syndromal model of schizophrenia and are likely to be of importance in furthering our understanding of its pathogenesis and in the development of suitable therapeutic strategies.

Contrast-enhanced MRI of the menisci of the knee using ultrashort echo time (UTE) pulse sequences: imaging of the red and white zones.

The objective of this study was to demonstrate the red and white zones of the meniscus of the knee using MRI. Ultrashort echo time (UTE) pulse sequences with an initial TE of 0.08 ms and later echoes at 5.95 ms, 11.08 ms and 17.70 ms were used to image the meniscus of the knee in two normal subjects before and after intravenous administration of gadodiamide. Difference images were formed by subtraction of later echo images from the first. The difference images showed obvious enhancement in an area consistent in location and dimensions with the red zone of the meniscus. Regions of interest placed within this area, central to it (corresponding to the white zone), and peripheral to it (corresponding to perimeniscal tissue) all showed increases in signal intensity after intravenous contrast administration. The greatest change in signal intensity in these regions of interest was seen with the shortest TE and in perimeniscal tissue on the original images. The increase in signal intensity was greatest in the red zone on the difference images. Using UTE pulse sequences and difference images derived from them, it is possible to visualize enhancement selectively in the red zone of the meniscus. Less obvious but significant changes in signal intensity were also present in the white zone.

Contrast enhancement of short T2 tissues using ultrashort TE (UTE) pulse sequences.

AIM: To review the effects of contrast administration on tissues with short T2s using a pulse ultrashort echo time (UTE) sequence. MATERIALS AND METHODS: Pulse sequences were implemented with echo times of 0.08 ms and three later gradient echoes. A fat-suppression option was used and later echo images were subtracted from the first echo image. Contrast enhancement with gadodiamide (0.3 mmol/kg) was used for serial studies in a volunteer. The images of 10 patients were reviewed for evidence of contrast enhancement in short T2 tissues. RESULTS: Contrast enhancement was seen in normal meninges, falx, tendons, ligaments, menisci, periosteum and cortical bone. In addition more extensive enhancement than with conventional pulse sequences was seen in meningeal disease, intervertebral disc disease, periligamentous scar tissue and periosteum after fracture. Subtraction of an image taken with a longer TE from the first image was of value in differentiating enhancement in short T2 tissues from that in long T2 tissues or blood. CONCLUSION: Contrast enhancement can be identified in tissues with short T2s using UTE pulse sequences in health and disease.

Magnetic resonance imaging of the Achilles tendon using ultrashort TE (UTE) pulse sequences.

AIM: To assess the potential value of imaging the Achilles tendon with ultrashort echo time (UTE) pulse sequences. MATERIALS AND METHODS: Four normal controls and four patients with chronic Achilles tendinopathy were examined in the sagittal and transverse planes. Three of the patients were examined before and after intravenous gadodiamide. RESULTS: The fascicular pattern was clearly demonstrated within the tendon and detail of the three distinct fibrocartilaginous components of an "enthesis organ" was well seen. T2* measurements showed two short T2* components. Increase in long T2 components with reduction in short T2 components was seen in tendinopathy. Contrast enhancement was much more extensive than with conventional sequences in two cases of tendinopathy but in a third case, there was a region of reduced enhancement. CONCLUSION: UTE pulse sequences provide anatomical detail not apparent with conventional sequences, demonstrate differences in T2* and show patterns of both increased and decreased enhancement in tendinopathy.

Ultrashort echo time (UTE) MRI of the spine in thalassaemia.

Back pain is common in adult patients with homozygous thalassaemia, and degenerative disc disease is increasingly recognised as a cause. Ultrashort echo time (UTE) pulse sequences, which are sensitive to the presence of short T(2) relaxation components in tissue produced by iron deposition and other processes, were used to examine the lower thoracic and lumbar spine in symptomatic patients with beta-thalassaemia major or intermedia. Three patients were studied with fat suppressed as well as both fat suppressed and long T(2) suppressed UTE (TE=0.08 ms) pulse sequences. Conventional 2D Fourier transformation T(1) and T(2) weighted scans were also performed for comparison. Normal controls showed narrow high signal areas in the region of the end-plate and annulus fibrosus. Patients showed hyperintense bands adjacent to the vertebral end plate in lower thoracic and lumbar spine discs using a UTE sequence with both long T(2) component and fat suppression. The extent of the changes was most marked in the patient with the most severe degenerative change. In the patient with minimal disease, findings of this type were present in discs which did not show evidence of degeneration with conventional MR imaging. High signal changes of a type previously not described were observed in each patient. The effect may be due to organic iron entering the disc and decreasing its T(1) and T(2), but susceptibility effects from iron in the vertebral bodies, fibrosis and other causes also need to be considered.

MRI of the brain with ultra-short echo-time pulse sequences.

As well as the long-T2 relaxation components normally detected with conventional imaging techniques, the brain has short-T2 components. We wished to use ultra-short (0.08 ms) echo time (UTE) pulse sequences to assess the feasibility of imaging these in normal subjects and patients. UTE sequences were employed, with or without fat suppression, 90 degree long-T2 suppression pulses, and selective nulling of long-T2 components using an inversion pulse. Subtraction of later echoes from the first was also used to reduce the signal from long-T2 components. We studied dive normal subjects and 15 patients with various diseases. Short-T2 components were demonstrated in grey and white matter. Increased signal from these components was seen in meningeal disease, probable calcification, presumed cavernomas, melanoma metastases and probable gliosis. Reduced signal was seen in some tumours, infarcts, mild multifocal vascular disease and vasogenic oedema. Further development and evaluation of these pulse sequences is warranted.

Magic angle imaging of the achilles tendon in patients with chronic tendonopathy.

AIMS: To assess the Achilles tendon in patients with chronic tendonopathy using magnetic resonance (MR) magic angle imaging, and to compare the appearances and uptake of contrast medium in abnormal tendons with those in normal tendons. MATERIAL AND METHODS: Eight patients with chronic Achilles tendonopathy and five normal controls were examined with the long axis of the tendon placed at 55 degrees and at 0 degrees to the main magnetic field. Conventional two-dimensional (2D) multi-slice images were obtained and T1 values were calculated before, and for up to 1h after the administration of intravenous gadodiamide. Both the unenhanced appearance and the pattern of enhancement in the tendon were compared. RESULTS: In the patients with tendonopathy, high signal intensity areas were evident on the short T1 inversion recovery (STIR) images obtained at 55 degrees in all tendons. Contrast medium enhancement was seen in six tendons and was most obvious on the images obtained at the magic angle. This was initially focal and then spread more diffusely within the tendon. After contrast medium administration, T1 values were significantly reduced in the tendonopathy group compared with normal controls (p<0.01). On the late post-contrast medium images obtained at 55 degrees, enhancement was evident in most of the tendon and correlated well with high signal intensity seen on STIR images. CONCLUSION: The use of magic angle MR imaging improved the demonstration of signal changes in the Achilles tendon in chronic tendonopathy. The STIR images obtained at the magic angle showed more obvious signal change than those obtained at 0 degrees. The changes due to enhancement were much more evident on images obtained at 55 degrees than at 0 degrees. The uptake of contrast medium was greater in the patients than in normal controls.

Magnetic resonance imaging of short T2 components in tissue.

The most widely used clinical magnetic resonance imaging techniques for the diagnosis of parenchymal disease employ heavily T(2)-weighted sequences to detect an increase or decrease in the signal from long T(2) components in tissue. Tissues also contain short T(2) components that are not detected or only poorly detected with conventional sequences. These components are the majority species in tendons, ligaments, menisci, periosteum, cortical bone and other related tissues, and the minority in many other tissues that have predominantly long T(2) components.The development and clinical application of techniques to detect short T(2) components are just beginning. Such techniques include magic angle imaging, as well as short echo time (TE), and ultrashort TE (Ute) pulse sequences. Magic angle imaging increases the T(2) of highly ordered, collagen-rich tissues such as tendons and ligaments so signal can be detected from them with conventional pulse sequences. Ute sequences detect short T(2) components before they have decayed, both in tissues with a majority of short T(2) components and those with a minority. In the latter case steps usually need to be taken to suppress the signal from the majority of long T(2) components. Fat suppression of different types may also be helpful. Once signal from short T(2) components has been detected, different pulse sequences can be used to determine increases or decreases in T(1) and T(2) and study contrast enhancement. Using these approaches, signals have been detected from normal tissues with a majority of short T(2) components such as tendons, ligaments, menisci, periosteum, cortical bone, dentine and enamel (the latter four tissues for the first time) as well as from the other tissues in which short T(2) components are a minority. Some diseases such as chronic fibrosis, gliosis, haemorrhage and calcification may increase the signal from short T(2) components while others such as loss of tissue, loss of order in tissue and an increase in water content may decrease them. Changes of these types have been demonstrated in tendonopathy, intervertebral disc disease, ligament injury, haemachromatosis, pituitary perivascular fibrosis, gliomas, multiple sclerosis and angiomas. Use of these techniques has reduced the limit of clinical detectability of short T(2) components by about two orders of magnitude from about 10 ms to about 100 micros. As a consequence it is now possible to study tissues that have a majority of short T(2) components with both "bright" and "dark" approaches, with the bright (high signal) approach offering options for developing tissue contrast of different types, as well as the potential for tissue characterization. In addition, tissues with a minority of short T(2) components may demonstrate changes in disease that are not apparent with conventional heavily T(2)-weighted sequences.

Subvoxel image registration of multislice (2D) magnetic resonance images in patients with high-grade gliomas of the brain.

AIMS: To implement a multislice two-dimensional (2D) T2-weighted sequence suitable for subvoxel image registration and to assess its usefulness in detecting change in high-grade intracranial gliomas. MATERIALS AND METHODS: Twenty patients with high-grade gliomas were studied on two or more occasions. T2-weighted multislice pulse sequences with a Gaussian slice profile, 50% overlapping slices and nearly isotropic voxels were acquired. The images were registered and subtraction images were produced. The images were compared with three-dimensional (3D) T1-weighted registered images and conventional unregistered T2-weighted images. All images were scored for changes in the lesions and ventricular system. RESULTS: The 2D and 3D registered subtraction images were the most sensitive for detecting changes in both the lesions and other regions in the brain. The mean rank scores were significantly higher for the lesions (chi2=86.742; df=5, n=38, P<0.0001) and for the ventricles (chi2=63.837; df=5, n=35, P<0.0001) compared with the unregistered and registered anatomical images. The subtraction images were also most sensitive for detecting signal intensity changes irrespective of the direction of change. CONCLUSION: Rigid body subvoxel registration can be successfully performed with both multislice 2D and 3D imaging. In principle, virtually all forms of clinical MR images of the brain can be accurately registered and subtracted.