Diffusion tensor invasive phenotypes can predict progression-free survival in glioblastomas.

INTRODUCTION: Glioblastomas multiformes (GBM) remain incurable in most cases. Their invasion into normal brain makes current therapies ineffective. Post-mortem studies suggest about a 25% of GBMs invade less than 1 cm from the tumour bulk and 20% invade more than 3 cm. AIM OF STUDY: The study aims to use DTI to assess tumour extension and determine how previously reported patterns relate to the progression-free survival (PFS). MATERIALS AND METHODS: Twenty-five patients with GBM treated according to the EORTC/NCIC protocol were retrospectively analysed. Patients were imaged post-operatively at 1.5 T. The sequences were composed of standard anatomical and a standard DTI sequence. As described earlier p and q maps were constructed. For each of the p and q maps, regions of interest were drawn around the visible abnormality. Patients were assigned a diffuse, localised or minimally invasive pattern. Progression was defined according to the RANO criteria (4) and PFS determined in days. Kaplan-Meier plots of survival for the three groups were plotted as were the proportion of patients who had not progressed at 24 months. RESULTS: The median PFS for the diffuse group was 278 days, for the localised group 605 days and 820 days for the minimally invasive group. Three-fourth of the minimally invasive group were progression-free at 24 months (LOG RANK 9.25; p = 0.010). CONCLUSION: It is possible to identify three invasive phenotypes in GBMs using Diffusion tensor imaging , and these three phenotypes have different progression free survival. A minimal phenotype (20% of patients) predicts a greater delay to progression.

High-resolution magnetic resonance imaging-based biomechanical stress analysis of carotid atheroma: a comparison of single transient ischaemic attack, recurrent transient ischaemic attacks, non-disabling stroke and asymptomatic patient groups.

BACKGROUND: Vulnerable carotid plaques are associated with cerebrovascular ischaemic events. High-resolution magnetic resonance (MR) imaging not only allows the morphological assessment of such plaques, but also provides geometrical data, which can be used for biomechanical stress analysis. We assess its utility to assess the plaque stress profiles of symptomatic (transient ischaemic attack (TIA) and non-disabling stroke) and asymptomatic patients. METHODS: A total of 70 consecutive patients with confirmed underlying carotid artery disease underwent carotid MR imaging of their carotid artery in a 1.5-T MR system using a standard carotid atheroma imaging protocol. MR images were manually segmented for different plaque components and used for biomechanical stress analysis. The maximum critical stress (M-CStress) for various clinical groups was determined and compared. RESULTS: M-CStress of symptomatic plaques (n = 45) was significantly higher than for asymptomatic plaques (n = 25) (median (interquartile range (IQR): 275 kPa (190-390) vs. 165 kPa (120-200), p = 0.0001)). Within the symptomatic group, no M-CStress differences were present between the TIA (n = 30) and stroke (n = 15) patients (260 kPa (190-370) vs. 295 kPa (200-510), p = 0.31). Within the TIA patient cohort, those who had presented with recurrent TIAs (n = 6) had significantly higher stresses than patients who had suffered a single episode (n = 24) (425 kPa (285-580) vs. 250 kPa (180-310), p = 0.001). CONCLUSIONS: Symptomatic carotid plaques, particularly those associated with recurrent TIAs, have high biomechanical stresses. As there is pre-existing evidence to suggest that high biomechanical stresses are associated with plaque vulnerability, MR-imaging-based stress analysis has the potential to identify high-risk patients with vulnerable plaques.

Ultrasmall superparamagnetic iron oxide-enhanced magnetic resonance imaging of abdominal aortic aneurysms--a feasibility study.

OBJECTIVES: Abdominal aortic aneurysms (AAAs), being predominantly atherosclerotic in nature, have underlying inflammatory activity. As it is well established that ultrasmall superparamagnetic iron oxide (USPIO) particles accumulate in the macrophages within atheromatous lesions, USPIO-enhanced magnetic resonance (MR) imaging can be potentially effective in the quantification of the associated inflammatory processes. METHODS: A total of 14 patients underwent USPIO-enhanced MR imaging using a 1.5T-MR system. Quantitative T(2)* and T(2) relaxation time data were acquired before and 36 h after UPSIO infusion at identical AAA locations. The pre- and post-USPIO-infusion relaxation times (T(2)(∗) and T(2)) were quantified and the correlation between pre- and post-USPIO infusion T(2)* and T(2) values was investigated. RESULTS: There was a significant difference between pre- and post-infusion T(2)* and T(2) values (both respective p-values = 0.005). A significant correlation between T(2)* and T(2) values post-USPIO infusion was observed (r = 0.90, p < 0.001), which indicates USPIO uptake by the aortic wall. CONCLUSIONS: Aortic wall inflammation using USPIO-enhanced MR imaging is feasible. Use of quantitative T(2) and T(2)* pulse sequences provides a quantitative method for assessing USPIO uptake by the aortic wall.

In vivo MRI-based 3D mechanical stress-strain profiles of carotid plaques with juxtaluminal plaque haemorrhage: an exploratory study for the mechanism of subsequent cerebrovascular events.

OBJECTIVES: Atherosclerotic plaque features, such as fibrous cap erosion, ulceration and rupture and presence of haemorrhage in carotid plaque are two important characteristics associated with subsequent cerebrovascular events and juxtaluminal haemorrhage/thrombus (JLH/T) indicates these two high-risk characteristics. This study aims to investigate the association between JLH/T and subsequent events in patients suffering from transient ischaemic attack (TIA). Three-dimensional mechanical analysis was employed to represent the critical mechanical stress (P-CStress) and stretch (P-CStretch) within the plaque. METHODS: Fifty TIA patients with mild-to-moderate carotid stenosis (30-69%) underwent high-resolution magnetic resonance imaging (MRI) within 72 h of the acute event and eight were excluded from the analysis due to various reasons. A total of 21 patients were found to have JLH/T in the carotid plaque and 21 did not (N-JLH/T). During a 2-year follow-up period, 11 (52.4%) patients in the JLH/T group experienced recurrent events and none in the N-JLH/T group. Three-dimensional plaque structure was reconstructed based on the in vivo MRI for the mechanical analysis. RESULTS: P-CStress of both groups was comparable (N-JLH/T: 174.45 ± 63.96 kPa vs. JLH/T: 212.60 ± 89.54 kPa; p = 0.120), but P-CStretch of JLH/T was significantly bigger than that of N-JLH/T (N-JLH/T: 1.21 ± 0.08 vs. JLH/T: 2.10 ± 0.53; p < 0.0001). Moreover, there were much bigger variations in stress and stretch of the JLH/T group during one cardiac cycle than in those of N-JLH/T group. CONCLUSIONS: In vivo MRI-depicted JLH/T might be a high risk factor initiating recurrent events, as big deformation appearing around the rupture site might prevent healing and tear the haemorrhage/thrombus away from the host structure and prompt further thrombo-embolic events.

Iron oxide particles for atheroma imaging.

The selection of patients for vascular interventions has been solely based on luminal stenosis and symptomatology. However, histological data from both the coronary and carotid vasculature suggest that other plaque features such as inflammation may be more important in predicting future thromboembolic events. Ultrasmall superparamagnetic iron oxide (USPIO) contrast agents have been used for noninvasive MRI assessment of atherosclerotic plaque inflammation in humans. It has reached the stage of development to have been recently used in an interventional drug study to not only assess inflammatory progression but also select patients at high risk. This article reviews the basic science behind the use of USPIO contrast agents in atheroma MR imaging, experimental work in animals, and how this has led to the emergence of this promising targeted imaging platform for assessment of high risk carotid atherosclerosis in humans.

Association between biomechanical structural stresses of atherosclerotic carotid plaques and subsequent ischaemic cerebrovascular events--a longitudinal in vivo magnetic resonance imaging-based finite element study.

BACKGROUND: High-resolution magnetic resonance (MR) imaging has been used for MR imaging-based structural stress analysis of atherosclerotic plaques. The biomechanical stress profile of stable plaques has been observed to differ from that of unstable plaques; however, the role that structural stresses play in determining plaque vulnerability remains speculative. METHODS: A total of 61 patients with previous history of symptomatic carotid artery disease underwent carotid plaque MR imaging. Plaque components of the index artery such as fibrous tissue, lipid content and plaque haemorrhage (PH) were delineated and used for finite element analysis-based maximum structural stress (M-C Stress) quantification. These patients were followed up for 2 years. The clinical end point was occurrence of an ischaemic cerebrovascular event. The association of the time to the clinical end point with plaque morphology and M-C Stress was analysed. RESULTS: During a median follow-up duration of 514 days, 20% of patients (n = 12) experienced an ischaemic event in the territory of the index carotid artery. Cox regression analysis indicated that M-C Stress (hazard ratio (HR): 12.98 (95% confidence interval (CI): 1.32-26.67, p = 0.02), fibrous cap (FC) disruption (HR: 7.39 (95% CI: 1.61-33.82), p = 0.009) and PH (HR: 5.85 (95% CI: 1.27-26.77), p = 0.02) are associated with the development of subsequent cerebrovascular events. Plaques associated with future events had higher M-C Stress than those which had remained asymptomatic (median (interquartile range, IQR): 330 kPa (229-494) vs. 254 kPa (166-290), p = 0.04). CONCLUSIONS: High biomechanical structural stresses, in addition to FC rupture and PH, are associated with subsequent cerebrovascular events.

Association between white matter ischaemia and carotid plaque morphology as defined by high-resolution in vivo MRI.

OBJECTIVES AND DESIGN: Both carotid plaque morphology and severity of white matter ischaemia (WMI) have been shown to be independent predictors of stroke risk. This study tests the hypothesis that there is an association between carotid plaque morphology as determined by high-resolution carotid MRI and WMI. MATERIALS AND METHODS: Forty patients (80 arteries) with at least 40% stenosis on screening Doppler ultrasound were recruited and underwent high-resolution axial carotid MRI at 1.5 T. In a blinded manner, plaque characteristics such as lipid core, fibrous cap, intraplaque haemorrhage, lumen area, plaque area, and American Heart Association (AHA) classification were qualitatively and quantitatively evaluated. The severity of WMI was independently quantified using a modified Scheltens score based on standard brain Fluid-Attenuated Inversion Recovery. Linear mixed effect models were used to test if carotid plaque characteristics could independently predict severity of WMI. RESULTS: Hypertension (p=0.005) and previous a history of transient ischaemic attack or stroke (p=0.038) were found to be significant predictors of severity of WMI. After accounting for confounding variables, no significant association was found between the modified Scheltens score and lipid core size (p=0.122), fibrous cap status (p=0.991), intraplaque haemorrhage (p=0.708), plaque area (0.835), lumen area (0.371) or an AHA Type VI complex plaque (p=0.195). CONCLUSIONS: Carotid plaque morphology as defined by MRI does not independently predict severity of WMI.

Temporal dependence of in vivo USPIO-enhanced MRI signal changes in human carotid atheromatous plaques.

INTRODUCTION: Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced MRI has been shown to be a useful modality to image activated macrophages in vivo, which are principally responsible for plaque inflammation. This study determined the optimum imaging time-window to detect maximal signal change post-USPIO infusion using T1-weighted (T1w), T2*-weighted (T2*w) and quantitative T2* (qT2*) imaging. METHODS: Six patients with an asymptomatic carotid stenosis underwent high resolution T1w, T2*w and qT2* MR imaging of their carotid arteries at 1.5 T. Imaging was performed before and at 24, 36, 48, 72 and 96 h after USPIO (Sinerem, Guerbet, France) infusion. Each slice showing atherosclerotic plaque was manually segmented into quadrants and signal changes in each quadrant were fitted to an exponential power function to model the optimum time for post-infusion imaging. RESULTS: The power function determining the mean time to convergence for all patients was 46, 41 and 39 h for the T1w, T2*w and qT2* sequences, respectively. When modelling each patient individually, 90% of the maximum signal intensity change was observed at 36 h for three, four and six patients on T1w, T2*w and qT2*, respectively. The rates of signal change decrease after this period but signal change was still evident up to 96 h. CONCLUSION: This study showed that a suitable imaging window for T1w, T2*w and qT2* signal changes post-USPIO infusion was between 36 and 48 h. Logistically, this would be convenient in bringing patients back for one post-contrast MRI, but validation is required in a larger cohort of patients.

Imaging regional variation of cellular proliferation in gliomas using 3'-deoxy-3'-[18F]fluorothymidine positron-emission tomography: an image-guided biopsy study.

AIM: To compare regional variations in uptake of 3'-deoxy-3'- [(18)F]-fluorothymidine (FLT) images using positron-emission tomography (PET) with measures of cellular proliferation from biopsy specimens obtained by image-guided brain biopsies. MATERIALS AND METHODS: Fourteen patients with a supratentorial glioma that required an image-guided brain biopsy were imaged preoperatively with dynamic PET after the administration of FLT. Maps of FLT irreversible uptake rate (K(i)) and standardized uptake value (SUV) were calculated. These maps were co-registered to a gadolinium-enhanced T1-weighted spoiled gradient echo (SPGR) sequence that was used for biopsy guidance, and the mean and maximum K(i) and SUV determined for each biopsy site. These values were correlated with the MIB-1 labelling index (a tissue marker of proliferation) from these biopsy sites. RESULTS: A total of 57 biopsy sites were studied. Although all measures correlated with MIB-1 labelling index, K(i)(max) provided the best correlation (Pearson coefficient, r=0.68; p<0.001). In low-grade gliomas the K(i)(mean) (+/-SD) was significantly higher than in normal tissue (3.3+/-1.7x10(-3)ml(plasma)/min/ml(tissue) versus 1.2+/-0.7x10(-3)ml(plasma)/min/ml(tissue); p=0.001). High-grade gliomas showed heterogeneous uptake with a mean K(i) of 7.7+/-4x10(-3)ml(plasma)/min/ml(tissue). A threshold K(i)(mean) of 1.8x10(-3) differentiates between normal tissue and tumour (sensitivity 84%, specificity 88%); however, the latter threshold underestimated the extent of tumour in half the cases. SUV closely agreed with K(i) measurements. CONCLUSION: FLT PET is a useful marker of cellular proliferation that correlates with regional variation in cellular proliferation; however, it is unable to identify the margin of gliomas.

Invasive and non-invasive modalities of imaging carotid stenosis.

Despite recent therapeutic advances, acute ischemic complications of atherosclerosis remain the primary cause of morbidity and mortality in Western countries, with carotid atherosclerotic disease one of the major preventable causes of stroke. As the impact of this disease challenges our healthcare systems, we are becoming aware that factors influencing this disease are more complex than previously realized. In current clinical practice, risk stratification relies primarily on evaluation of the degree of luminal stenosis and patient symptomatology. Adequate investigation and optimal imaging are important factors that affect the quality of a carotid endarterectomy (CEA) service and are fundamental to patient selection. Digital subtraction angiography is still perceived as the most accurate imaging modality for carotid stenosis and historically has been the cornerstone of most of the major CEA trials but concerns regarding potential neurological complications have generated substantial interest in non-invasive modalities, such as contrast-enhanced magnetic resonance angiography. The purpose of this review is to give an overview to the vascular specialist of the current imaging modalities in clinical practice to identify patients with carotid stenosis. Advantages and disadvantages of each technique are outlined. Finally, limitations of assessing luminal stenosis in general are discussed. This article will not cover imaging of carotid atheroma morphology, function and other emerging imaging modalities of assessing plaque risk, which look beyond simple luminal measurements.

Characterisation of carotid atheroma in symptomatic and asymptomatic patients using high resolution MRI.

BACKGROUND AND PURPOSE: To prospectively evaluate differences in carotid plaque characteristics in symptomatic and asymptomatic patients using high resolution MRI. METHODS: 20 symptomatic and 20 asymptomatic patients, with at least 50% carotid stenosis as determined by Doppler ultrasound, underwent preoperative in vivo multispectral MRI of the carotid arteries. Studies were analysed both qualitatively and quantitatively in a randomised manner by two experienced readers in consensus, blinded to clinical status, and plaques were classified according to the modified American Heart Association (AHA) criteria. RESULTS: After exclusion of poor quality images, 109 MRI sections in 18 symptomatic and 19 asymptomatic patients were available for analysis. There were no significant differences in mean luminal stenosis severity (72.9% vs 67.6%; p = 0.09) or plaque burden (median plaque areas 50 mm(2) vs 50 mm(2); p = 0.858) between the symptomatic and asymptomatic groups. However, symptomatic lesions had a higher incidence of ruptured fibrous caps (36.5% vs 8.7%; p = 0.004), haemorrhage or thrombus (46.5% vs 14.0%; p<0.001), large necrotic lipid cores (63.8% vs 28.0%; p = 0.002) and complicated type VI AHA lesions (61.5% vs 28.1%; p = 0.001) compared with asymptomatic lesions. The MRI findings of plaque haemorrhage or thrombus had an odds ratio of 5.25 (95% CI 2.08 to 13.24) while thin or ruptured fibrous cap (as opposed to a thick fibrous cap) had an odds ratio of 7.94 (95% CI 2.93 to 21.51) for prediction of symptomatic clinical status. CONCLUSIONS: There are significant differences in plaque characteristics between symptomatic and asymptomatic carotid atheroma and these can be detected in vivo by high resolution MRI.

Combined PET-FDG and USPIO-enhanced MR imaging in patients with symptomatic moderate carotid artery stenosis.

INTRODUCTION: PET-FDG and USPIO-enhanced MRI are increasingly being used in depicting carotid atheroma inflammation--a risk factor for the high risk plaque. Their combined use has not been previously reported. REPORT: Two patients presenting with stroke and identified with 50% carotid stenosis on duplex ultrasonography, underwent PET FDG and USPIO-enhanced MR imaging. Results were concordant and complementary suggesting that both techniques reflect similar metabolic processes. DISCUSSION: The selection of patients for carotid revascularisation has largely been based on the severity of luminal stenosis alone. The two imaging modalities, which identify inflammatory activity, may be potential surrogate risk markers in the selection of patients eligible for carotid surgery, if plaque inflammation can be correlated with risk of developing clinical symptoms.

Comparison of the inflammatory burden of truly asymptomatic carotid atheroma with atherosclerotic plaques in patients with asymptomatic carotid stenosis undergoing coronary artery bypass grafting: an ultrasmall superparamagnetic iron oxide enhanced magnetic resonance study.

INTRODUCTION: Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. The aim of this study was to explore whether there is a difference in the degree of Magnetic Resonance (MR) defined inflammation using Ultra Small Super-Paramagnetic Iron Oxide (USPIO) particles, within carotid atheroma in completely asymptomatic individuals and the asymptomatic carotid stenosis in a cohort of patients undergoing coronary artery bypass grafting (CABG). METHODS: 10 patients awaiting CABG with asymptomatic carotid disease and 10 completely asymptomatic individuals with no documented coronary artery disease underwent multi-sequence MR imaging before and 36 hours post USPIO infusion. Images were manually segmented into quadrants and signal change in each quadrant, normalised to adjacent muscle signal, was calculated following USPIO administration. RESULTS: The mean percentage of quadrants showing signal loss was 94% in the CABG group, compared to 24% in the completely asymptomatic individuals (p<0.001). The carotid plaques from the CABG patients showed a significant mean signal intensity decrease of 16.4% after USPIO infusion (95% CI 10.6% to 22.2%; p<0.001). The truly asymptomatic plaques showed a mean signal intensity increase (i.e. enhancement) after USPIO infusion of 8.4% (95% CI 2.6% to 14.2%; p=0.007). The mean signal difference between the two groups was 24.9% (95% CI 16.7% to 33.0%; p<0.001). CONCLUSIONS: These findings are consistent with the hypothesis that inflammatory atheroma is a systemic disease. The carotid territory is more likely to take up USPIO if another vascular territory is symptomatic.

Early radiotherapy dose response and lack of hypersensitivity effect in normal brain tissue: a sequential dynamic susceptibility imaging study of cerebral perfusion.

AIMS: To determine if magnetic resonance perfusion markers can be used as an analytical marker of subclinical normal brain injury after radiotherapy, by looking for a dose-effect relationship. MATERIALS AND METHODS: Four patients undergoing conformal radiotherapy to 54Gy in 30 fractions for low-grade gliomas were imaged with conventional T(2)-weighted and fluid attenuated inversion recovery imaging as well as dynamic contrast susceptibility perfusion imaging. Forty regions of interest were determined from the periventricular white matter. All conventional sequences were examined for evidence of radiation-induced changes. Patients were imaged before radiotherapy, after one fraction, at the end of treatment and then at 1 and 3 months from the end of radiotherapy. For each region the relative cerebral blood volume (rCBV), relative cerebral blood flow (rCBF) and mean transit time (MTT) expressed as a ratio of the baseline value, and radiotherapy dose were determined. RESULTS: Of the 40 regions, seven occurred within the gross tumour volume and a further four occurred in regions later infiltrated by tumour, and were thus excluded. Regions within the 80% isodose showed a reduction in rCBV and rCBF over the 3 month period. There was no significant alteration in rCBV or rCBF in regions outside the 60% isodose (i.e. <32Gy). MTT did not alter in any region. There seemed to be a threshold effect at 132 days from the end of radiotherapy of 47% (standard error of the mean 11.5, about 25.4Gy) for rCBV and 59% (standard error of the mean 14.2, about 31.9Gy) for rCBF. CONCLUSIONS: There was a dose-related reduction in rCBV and rCBF in normal brain after radiotherapy at higher dose levels. Although this study used a limited number of patients, it suggests that magnetic resonance perfusion imaging seems to act as a marker of subclinical response of normal brain and that there is an absence of an early hypersensitivity effect with small doses per fraction. Further studies are required with larger groups of patients to show that these results are statistically robust.

Can MRI Visual Assessment Differentiate the Variants of Primary-Progressive Aphasia?

BACKGROUND AND PURPOSE: Primary-progressive aphasia is a clinically and pathologically heterogeneous condition. Nonfluent, semantic, and logopenic are the currently recognized clinical variants. The recommendations for the classification of primary-progressive aphasia have advocated variant-specific patterns of atrophy. The aims of the present study were to evaluate the sensitivity and specificity of the proposed imaging criteria and to assess the intra- and interrater reporting agreements. MATERIALS AND METHODS: The cohort comprised 51 patients with a root diagnosis of primary-progressive aphasia, 25 patients with typical Alzheimer disease, and 26 matched control participants. Group-level analysis (voxel-based morphometry) confirmed the proposed atrophy patterns for the 3 syndromes. The individual T1-weighted anatomic images were reported by 3 senior neuroradiologists. RESULTS: We observed a dichotomized pattern of high sensitivity (92%) and specificity (93%) for the proposed atrophy pattern of semantic-variant primary-progressive aphasia and low sensitivity (21% for nonfluent-variant primary-progressive aphasia and 43% for logopenic-variant primary-progressive aphasia) but high specificity (91% for nonfluent-variant primary-progressive aphasia and 95% for logopenic-variant primary-progressive aphasia) in other primary-progressive aphasia variants and Alzheimer disease (sensitivity 43%, specificity 92%). MR imaging was least sensitive for the diagnosis of nonfluent-variant primary-progressive aphasia. Intrarater agreement analysis showed mean κ values above the widely accepted threshold of 0.6 (mean, 0.63 ± 0.16). Pair-wise interobserver agreement outcomes, however, were well below this threshold in 5 of the 6 possible interrater contrasts (mean, 0.41 ± 0.09). CONCLUSIONS: While the group-level results were in precise agreement with the recommendations, semantic-variant primary-progressive aphasia was the only subtype for which the proposed recommendations were both sensitive and specific at an individual level.

Imaging Carotid Atherosclerosis Plaque Ulceration: Comparison of Advanced Imaging Modalities and Recent Developments.

Atherosclerosis remains the leading cause of long-term mortality and morbidity worldwide, despite remarkable advancement in its management. Vulnerable atherosclerotic plaques are principally responsible for thromboembolic events in various arterial territories such as carotid, coronary, and lower limb vessels. Carotid plaque ulceration is one of the key features associated with plaque vulnerability and is considered a notable indicator of previous plaque rupture and possible future cerebrovascular events. Multiple imaging modalities have been used to assess the degree of carotid plaque ulceration for diagnostic and research purposes. Early diagnosis and management of carotid artery disease could prevent further cerebrovascular events. In this review, we highlight the merits and limitations of various imaging techniques for identifying plaque ulceration.

Improved delineation of glioma margins and regions of infiltration with the use of diffusion tensor imaging: an image-guided biopsy study.

BACKGROUND AND PURPOSE: The efficacy of radiation therapy, the mainstay of treatment for malignant gliomas, is limited by our inability to accurately determine tumor margins. As a result, despite recent advances, the prognosis remains appalling. Because gliomas preferentially infiltrate along white matter tracks, methods that show white matter disruption should improve this delineation. In this study, results of histologic examination from samples obtained from image-guided brain biopsies were correlated with diffusion tensor images. METHODS: Twenty patients requiring image-guided biopsies for presumed gliomas were imaged preoperatively. Patients underwent image-guided biopsies with multiple biopsies taken along a single track that went into normal-appearing brain. Regions of interest were determined from the sites of the biopsies, and diffusion tensor imaging findings were compared with glioma histology. RESULTS: Using diffusion tissue signatures, it was possible to differentiate gross tumor (reduction of the anisotropic component, q > 12% from contralateral region), from tumor infiltration (increase in the isotropic component, p > 10% from contralateral region). This technique has a sensitivity of 98% and specificity of 81%. T2-weighted abnormalities failed to identify the margin in half of all specimens. CONCLUSION: Diffusion tensor imaging can better delineate the tumor margin in gliomas. Such techniques can improve the delineation of the radiation therapy target volume for gliomas and potentially can direct local therapies for tumor infiltration.

Physiological thresholds for irreversible tissue damage in contusional regions following traumatic brain injury.

Cerebral ischaemia appears to be an important mechanism of secondary neuronal injury in traumatic brain injury (TBI) and is an important predictor of outcome. To date, the thresholds of cerebral blood flow (CBF) and cerebral oxygen utilization (CMRO(2)) for irreversible tissue damage used in TBI studies have been adopted from experimental and clinical ischaemic stroke studies. Identification of irreversibly damaged tissue in the acute phase following TBI could have considerable therapeutic and prognostic implications. However, it is questionable whether stroke thresholds are applicable to TBI. Therefore, the aim of this study was to determine physiological thresholds for the development of irreversible tissue damage in contusional and pericontusional regions in TBI, and to determine the ability of such thresholds to accurately differentiate irreversibly damaged tissue. This study involved 14 patients with structural abnormalities on late-stage MRI, all of whom had been studied with (15)O PET within 72 h of TBI. Lesion regions of interest (ROI) and non-lesion ROIs were constructed on late-stage MRIs and applied to co-registered PET maps of CBF, CMRO(2) and oxygen extraction fraction (OEF). From the entire population of voxels in non-lesion ROIs, we determined thresholds for the development of irreversible tissue damage as the lower limit of the 95% confidence interval for CBF, CMRO(2) and OEF. To test the ability of a physiological variable to differentiate lesion and non-lesion tissue, we constructed probability curves, demonstrating the ability of a physiological variable to predict lesion and non-lesion outcomes. The lower limits of the 95% confidence interval for CBF, CMRO(2) and OEF in non-lesion tissue were 15.0 ml/100 ml/min, 36.7 mumol/100 ml/min and 25.9% respectively. Voxels below these values were significantly more frequent in lesion tissue (all P < 0.005, Mann-Whitney U-test). However, a significant proportion of lesion voxels had values above these thresholds, so that definition of the full extent of irreversible tissue damage would not be possible based upon single physiological thresholds. We conclude that, in TBI, the threshold of CBF below which irreversible tissue damage consistently occurs differs from the classical CBF threshold for stroke (where similar methodology is used to define such thresholds). The CMRO(2) threshold is comparable to that reported in the stroke literature. At a voxel-based level, however (and in common with ischaemic stroke), the extent of irreversible tissue damage cannot be accurately predicted by early abnormalities of any single physiological variable.

Enhanced visualization and quantification of magnetic resonance diffusion tensor imaging using the p:q tensor decomposition.

Many scalar measures have been proposed to quantify magnetic resonance diffusion tensor imaging (MR DTI) data in the brain. However, only two parameters are commonly used in the literature: mean diffusion (D) and fractional anisotropy (FA). We introduce a visualization technique which permits the simultaneous analysis of an additional five scalar measures. This enhanced diversity is important, as it is not known a priori which of these measures best describes pathological changes for brain tissue. The proposed technique is based on a tensor transformation, which decomposes the diffusion tensor into its isotropic (p) and anisotropic (q) components. To illustrate the use of this technique, diffusion tensor imaging was performed on a healthy volunteer, a sequential study in a patient with recent stroke, a patient with hydrocephalus and a patient with an intracranial tumour. Our results demonstrate a clear distinction between different anatomical regions in the normal volunteer and the evolution of the pathology in the patients. In the normal volunteer, the brain parenchyma values for p and q fell into a narrow band with 0.976