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.

Advances in MRI for the evaluation of carotid atherosclerosis.

Carotid artery atherosclerosis is an important source of mortality and morbidity in the Western world with significant socioeconomic implications. The quest for the early identification of the vulnerable carotid plaque is already in its third decade and traditional measures, such as the sonographic degree of stenosis, are not selective enough to distinguish those who would really benefit from a carotid endarterectomy. MRI of the carotid plaque enables the visualization of plaque composition and specific plaque components that have been linked to a higher risk of subsequent embolic events. Blood suppressed T1 and T2 weighted and proton density-weighted fast spin echo, gradient echo and time-of-flight sequences are typically used to quantify plaque components such as lipid-rich necrotic core, intraplaque haemorrhage, calcification and surface defects including erosion, disruption and ulceration. The purpose of this article is to review the most important recent advances in MRI technology to enable better diagnostic carotid imaging.

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.

Signal-to-noise ratio increase in carotid atheroma MRI: a comparison of 1.5 and 3 T.

OBJECTIVES: This study reports quantitative comparisons of signal-to-noise ratio (SNR) at 1.5 and 3 T from images of carotid atheroma obtained using a multicontrast, cardiac-gated, blood-suppressed fast spin echo protocol. METHODS: 18 subjects, with carotid atherosclerosis (>30% stenosis) confirmed on ultrasound, were imaged on both 1.5 and 3 T systems using phased-array coils with matched hardware specifications. T(1) weighted (T(1)W), T(2) weighted (T(2)W) and proton density-weighted (PDW) images were acquired with identical scan times. Multiple slices were prescribed to encompass both the carotid bifurcation and the plaque. Image quality was quantified using the SNR and contrast-to-noise ratio (CNR). A phantom experiment was also performed to validate the SNR method and confirm the size of the improvement in SNR. Comparisons of the SNR values from the vessel wall with muscle and plaque/lumen CNR measurements were performed at a patient level. To account for the multiple comparisons a Bonferroni correction was applied. RESULTS: One subject was excluded from the protocol owing to image quality and protocol failure. The mean improvement in SNR in plaque was 1.9, 2.1 and 2.1 in T(1)W, T(2)W and PDW images, respectively. All plaque SNR improvements were statistically significant at the p<0.05 level. The phantom experiment reported an improvement in SNR of 2.4 for PDW images. CONCLUSIONS: Significant gains in SNR can be obtained for carotid atheroma imaging at 3 T compared with 1.5 T. There was also a trend towards increased CNR. However, this was not significant after the application of the Bonferroni correction.

MR angiography and imaging for the evaluation of middle cerebral artery atherosclerotic disease.

Intracranial atherosclerotic disease may constitute the most common cause of ischemic stroke worldwide; yet, in the developed world, imaging research has largely focused on extracranial atherosclerosis. Many studies in populations of Asian, African, and Hispanic descent demonstrate the preponderance of intracranial stenosis compared with carotid stenosis. This review examines the clinical presentations of MCA atherosclerosis and stenosis and the use of noninvasive MR imaging in the assessment of intracranial vasculature. MRA is a well-validated technique that offers great advantage over traditional angiography. Advances in high-resolution MR imaging of MCA stenosis have the potential to yield excellent visualization of plaque. Future developments in high-resolution MR imaging to depict intracranial atherosclerosis are explored in this review; these advances will guide endovascular therapy and the comparison of novel interventions.

Noninvasive carotid artery imaging with a focus on the vulnerable plaque.

Currently carotid imaging has 2 main focuses: assessment of luminal stenosis and classification of atherosclerotic plaque characteristics. Measurement of the degree of stenosis is the main assessment used for current treatment decision making, but an evolving idea that is now driving imaging is the concept of vulnerable plaque, which is where plaque components are identified and used to define which plaques are at high risk of causing symptoms compared with those at low risk. This review article covers the methods used for noninvasive assessment of carotid luminal stenosis and the options available for plaque imaging.

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.

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.

Methodology of diffusion-weighted, diffusion tensor and magnetisation transfer imaging.

MRI offers a number of opportunities to examine characteristics of tissue well below the spatial resolution of the imaging technique. The best known of these is diffusion imaging, which allows the production of images whose contrast reflects the ability of water molecules to move through the extravascular extracellular space. Less well-known, but increasingly important, is magnetisation transfer imaging, which produces contrast based on the ability of protons to move between the free water pool and local macromolecules. Both of these techniques offer unique information about the microscopic and molecular structure of tumour tissue. This article will briefly review the underlying theory and technical aspects associated with these imaging techniques.

Imaging biomarkers of brain tumour margin and tumour invasion.

Invasion of tumour cells into the normal brain is one of the major reasons of treatment failure for gliomas. Although there is a good understanding of the molecular and cellular processes that occur during this invasion, it is not possible to detect the extent of the tumour with conventional imaging. However, there is an understanding that the degree of invasion differs with individual tumours, and yet they are all treated the same. Newer imaging techniques that probe the pathological changes within tumours may be suitable biomarkers for invasion. Imaging methods are now available that can detect subtle changes in white matter organisation (diffusion tensor imaging), tumour metabolism and cellular proliferation (using MR spectroscopy and positron emission tomography) occurring in regions of tumour that cannot be detected by conventional imaging. The role of such biomarkers of invasion should allow better delineation of tumour margins, which should improve treatment planning (especially surgery and radiotherapy) and provide information on the invasiveness of an individual tumour to help select the most appropriate therapy and help stratify patients for clinical trials.

Correlation of MR relative cerebral blood volume measurements with cellular density and proliferation in high-grade gliomas: an image-guided biopsy study.

BACKGROUND AND PURPOSE: As newer MR imaging techniques are used to assist with tumor grading, biopsy planning, and therapeutic response assessment, there is a need to relate the imaging characteristics to underlying pathologic processes. The aim of this study was to see how rCBV, a known marker of tumor vascularity, relates to cellular packing attenuation and cellular proliferation. MATERIALS AND METHODS: Nine patients with histologically proved high-grade gliomas and 1 with a supratentorial PNET requiring an image-guided biopsy were recruited. Patients underwent a DSC study. The rCBV at the intended biopsy sites was determined by using a histogram measure to derive the mean, maximum, and 75th centile and 90th centile values. This measure was correlated with histologic markers of the MIB-1 labeling index (as a marker of glioma cell proliferation) and the total number of neoplastic cells in a high-power field (cellular packing attenuation). RESULTS: There was a good correlation between rCBV and MIB-1 by using all the measures of rCBV. The mean rCBV provided the best results (r = 0.66, P < .001). The only correlation with cellular packing attenuation was with the 90% centile (rCBV(90%), r = 0.36, P = .03). The increase in rCBV could be seen over 1 cm from the edge of enhancement in 4/10 cases, and at 2 cm in 1/10. CONCLUSIONS: rCBV correlated with cellular proliferation in high-grade gliomas but not with cellular packing attenuation. The increase in rCBV extended beyond the contrast-enhancing region in 50% of our patients.

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.

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.

Experimental measurement of the mechanical properties of carotid atherothrombotic plaque fibrous cap.

Eleven carotid atherothrombotic plaque samples were harvested from patients. Three samples that were highly calcified were discarded, while eight yielded results. The elastic properties of the material were estimated by fitting the measured indentation response to finite element simulations. The methodology was refined and its accuracy quantified using a synthetic rubber. The neo-Hookean form of the material model gave a good fit to the measured response of the tissue. The inferred shear modulus mu was found to be in the range 7-100 kPa, with a median value of 11 kPa. A review of published materials data showed a wide range of material properties for human atherothrombotic tissue. The effects of anisotropy and time dependency in these published results were highlighted. The present measurements were comparable to the static radial compression tests of Lee et al, 1991 [Structure-dependent dynamic behaviour of fibrous caps from human atherosclerotic plaques. Circulation 83, 1764-1770].

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.

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.