Anne L. Martel

Characterization of Complicated Carotid Plaque With Magnetic Resonance Direct Thrombus Imaging in Patients With Cerebral Ischemia

Background Thromboembolic disease secondary to complicated carotid atherosclerotic plaque is a major cause of cerebral ischemia. Clinical management relies on the detection of significant (>70%) carotid stenosis. A large proportion of patients suffer irreversible cerebral ischemia as a result of lesser degrees of stenosis. Diagnostic techniques that can identify nonstenotic high‐risk plaque would therefore be beneficial. High‐risk plaque is defined histologically if it contains hemorrhage/thrombus. Magnetic resonance direct thrombus imaging (MRDTI) is capable of detecting methemoglobin within intraplaque hemorrhage. We assessed this as a marker of complicated plaque and compared its accuracy with histological examination of surgical endarterectomy specimens. Methods and Results Sixty‐three patients underwent successful MRDTI and endarterectomy with histological examination. Of these, 44 were histologically defined as complicated (type VI plaque). MRDTI demonstrated 3 false‐positive and 7 false‐negative results, giving a sensitivity and specificity of 84%, negative predictive value of 70%, and positive predictive value of 93%. The interobserver (κ=0.75)and intraobserver (κ=0.9) agreement for reading MRDTI scans was good. Conclusions MRDTI of the carotid vessels in patients with cerebral ischemia is an accurate means of identifying histologically confirmed complicated plaque. The high contrast generated by short T1 species within the plaque allows for ease of interpretation, making this technique highly applicable in the research and clinical setting for the investigation of carotid atherosclerotic disease. (Circulation. 2003;107:3047‐3052.)

Diagnosis of Lower-Limb Deep Venous Thrombosis: A Prospective Blinded Study of Magnetic Resonance Direct Thrombus Imaging

Despite considerable recent advances in diagnostic techniques for lower-limb deep venous thrombosis (DVT), current methods have disadvantages. Ultrasonography, the most accurate noninvasive test, is widely available and cheap. As such, it has largely replaced venography as the test of first choice for symptomatic DVT. In a recent meta-analysis, the sensitivity of ultrasonography was 89% overall for symptomatic DVT and 97% for above-knee thrombosis (1). Large outcome studies have shown that patients may be safely left untreated after a negative result on ultrasonography if they have a low clinical risk score, a low d-dimer level, or a negative result on repeated ultrasonography at 1 week (2-4). However, these strategies may be complex and still require 3% to 34% of outpatients and most inpatients to undergo repeated ultrasonography at 1 week (2-4). In practice, retesting after 1 week is inconvenient, and physicians often rely on a single test or request immediate venography (5). Other problems with ultrasonography include poor sensitivity for asymptomatic disease, difficulties in diagnosing DVT recurrence, and limited visualization in the pelvis (1, 6, 7). Impedance plethysmography is also commonly used; however, it has a lower diagnostic accuracy than ultrasonography and has similar weaknesses in the setting of recurrent thrombosis, asymptomatic DVT, and DVT below the knee or in the pelvis (1, 4, 6). Computed tomography and magnetic resonance imaging techniques can visualize DVT above the knee and in the pelvis but in general are unsuccessful below the knee (8-10). The ability of these techniques to diagnose DVT recurrence and asymptomatic disease has not been tested. Venography is the reference standard diagnostic test, but it has in large part been replaced by noninvasive tests. In clinical practice, it is the most reliable test for the diagnosis of asymptomatic thrombosis and thrombosis isolated within the calf or pelvis. However, imaging in the pelvis is inadequate in up to 24% of normal studies, and the proximal extent of thrombosis is frequently not delineated in patients with above-knee DVT (11). Underfilling of vessels and vessels overlying one another also create problems with venography below the knee. Studies have shown that interobserver variability for venography is high (10% to 16%), especially below the knee ( = 0.46 to 0.73 below the knee and 0.46 to 0.84 above the knee) (12, 13). In addition, a high proportion of studies are nondiagnostic for possible DVT recurrence (1, 6). A noninvasive test is needed that accurately diagnoses above-knee DVT and thrombus below the knee, in the pelvis, and in asymptomatic limbs. Unlike most imaging techniques, which identify thrombus as filling defects, magnetic resonance direct thrombus imaging (MRDTI) visualizes thrombus against a suppressed background (14). In an unblinded comparison with venography, we previously showed that MRDTI precisely visualizes acute deep venous thrombus (14, 15). In the current study, we sought to assess prospectively whether MRDTI is a reliable diagnostic test for suspected acute symptomatic DVT. Methods The ethics committee at our institution granted approval for the study, and all participants gave written informed consent. With the exceptions of pregnant women, patients with known contrast allergy, and those with renal failure, all patients with DVT suspected on the basis of lower limb symptoms are investigated by using venography at our institution. Participants were recruited after routine venography was done between May 1998 and September 1999. During this time, 338 consecutive patients underwent routine contrast venography. Consecutive patients with positive venograms were selected, along with one quarter of those with negative venograms, according to a predetermined random sequence. This protocol was chosen to equalize the numbers of positive and negative cases and was based on a 6-month audit of venograms in our institution that found that 22% of venograms were positive. Clinical diagnostic criteria were not used, and the decision to request investigation for suspected DVT had been made by the attending clinician; however, patients who did not have leg symptoms were not recruited. Other exclusion criteria were failed or inconclusive venography, failed or inconclusive MRDTI, contraindications to MRI, and claustrophobia (Figure 1). Individual venous segments that were nondiagnostic at venography were also excluded from analysis. Figure 1. Outline of the study. Magnetic resonance direct thrombus imaging was performed on all patients recruited within 48 hours of venography. The scans were interpreted by an experienced radiologist (reviewer A) and by a nonradiologist (reviewer B) trained to read MRDTI scans. For venograms and MRDTI scans, the reviewers noted the presence or absence of DVT; the diagnostic classification of DVT, divided into isolated calf DVT, femoropopliteal DVT, and ileofemoral DVT; and the presence of thrombus in the calf, femoropopliteal, and iliac venous segments. Venograms were obtained and initially reported by the radiologists on duty. This initial report was used to make recruitment decisions; if the results were discordant with those of MRDTI, ultrasonography was also performed. However, ultrasonography was not used in the calculations of the accuracy of MRDTI. After completion of the study, venograms were interpreted by an independent radiologist, and these results were used as the gold standard against which MRDTI was compared. Results of MRDTI and venography were reported without knowledge of the results of other tests and the other readings. The d-dimer level was measured in all patients at the time of the MRDTI scan by using the Nycocard (Nycomed Pharma AS, Asker, Norway) technique (normal level < 0.3 mg/L). Venography Venography was performed by cannulating a dorsal pedal vein with a 21-gauge needle and rapidly injecting 50 to 100 mL of iodinated contrast medium (I2, 300 mg/mL), with the patient supine and tilted 30 degrees with his or her feet downward. A tourniquet was applied above the ankle. Anteroposterior and two oblique views of the deep calf and popliteal veins were obtained. Views of the femoral and iliac veins were then obtained. The study result was considered positive if intraluminal filling defects were seen or persistent nonfilling of veins with a sharp cut-off was detected. Magnetic Resonance Imaging Magnetic resonance imaging was performed by using a 1.5-Tesla unit (Siemens Vision, Erlangen, Germany) with a T1-weighted magnetization-prepared three-dimensional gradient-echo sequence. The sequence included a water-only excitation radiofrequency pulse to abolish the fat signal, and the effective inversion time was chosen to nullify the blood signal. Imaging was performed from the ankle to the inferior vena cava in two imaging blocks with a total acquisition time of 12 minutes by using a 55-cm body coil. Both legs were imaged simultaneously. Scanning was performed by radiographers in all cases. Image assessment involved reading of coronal source data and standard image reconstruction techniques. Acute thrombus was diagnosed on the basis of its high signal against the suppressed background (Figure 2). Figure 2. Magnetic resonance direct thrombus imaging in three patients. A. arrows B. arrows C. single arrows double arrow Ultrasonography Color flow and compression ultrasonographic images of the symptomatic limb from the common femoral vein distally were obtained by using a 5-MHz linear array transducer. As much of the superficial femoral vein as possible was imaged, together with the popliteal vein and the calf veins. Augmentation of flow was used to verify patency. Examinations were performed by senior radiologists, and DVT was confirmed in all cases by noncompressibility on gray-scale images. The sonographer was unaware of the other test results, but in cases of possible isolated calf thrombosis, he or she was told to concentrate the examination below the knee to maximize accuracy in this region. Statistical Analysis Sensitivity and specificity were calculated for the overall diagnosis of DVT; diagnosis of isolated calf DVT, femoropopliteal DVT, and ileofemoral DVT; and presence of thrombus in the calf, femoropopliteal vein, and iliac vein. Exact CIs were calculated. Interobserver error was calculated for these observations by using the weighted statistic with equally spaced weights for positive, nondiagnostic, and negative studies. Confidence intervals for the statistic were calculated from asymptotic estimations of the standard error. Calculations were performed by using SPSS software (SPSS, Inc., Chicago, Illinois). Results One hundred four patients were recruited according to our protocol (Figure 1). The time between venography and MRDTI was less than 8 hours in 28 patients, 8 to 24 hours in 44 patients, and 24 to 48 hours in 32 patients. Age ranged from 20 to 95 years, and symptom onset varied from 1 to 35 days. Ninety-five patients were referred from medical specialties and 9 from surgical specialties; 47 were inpatients and 57 were outpatients. Both reviewers reported that 3 of 5 patients with ipsilateral total hip replacements had nondiagnostic MRDTI scans. Venography diagnosed femoropopliteal DVT in 1 of these patients and was negative in 2 patients. These 3 patients were excluded from further analysis, leaving 101 patients in the study. One patient could tolerate only the first scanning block from ankle to thigh level owing to claustrophobia; however, femoropopliteal DVT could still be diagnosed. All other patients tolerated MRI. Eighteen of 148 patients (12%) were excluded from the study. Fifteen patients could not undergo MRI because of contraindications (9 patients) or claustrophobia (6 patients), and 3 patients had inconclusive results on MRDTI. Venography failed (29 patients) or was inconclusive (11 patients) in 12% of patients (40 of 338). Venography was inconclusive

Prolonged hemiplegic migraine associated with unilateral hyperperfusion on perfusion weighted magnetic resonance imaging

Hemiplegic migraine (HM) is an unusual subset of migraine with aura, in which headache is associated with unilateral motor deficits, thought to be attributable to an underlying calcium channelopathy.1 In some cases the neurological dysfunction may outlast the headache and persist for many days. In the initial stages, hemiplegic migraine may mimic cerebral infarction. Within the first few hours after stroke, both computed tomography and magnetic resonance imaging (MRI) are often normal. However, more information can be gained using diffusion (DWI) and perfusion weighted imaging (PWI), which are much more sensitive to acute events in cerebral ischaemia. A recently reported post-processing technique (factor analysis of dynamic studies FADS) can be applied to PWI to generate images representing arterial (“early”) and venous (“late”) contributions to signal intensity.2 This report outlines the findings arising from the application of multimodal MRI techniques to a patient with prolonged hemiplegic migraine. A 21 year old woman, with a long history of familial HM, presented with a six hour history of headache, nausea, right sided weakness, and expressive dysphasia. Her maternal aunt had also suffered with …

Extracting parametric images from dynamic contrast-enhanced MRI studies of the brain using factor analysis

Factor analysis of dynamic studies (FADS) is a technique that allows structures with different temporal characteristics to be extracted from dynamic contrast enhanced studies without making any a priori assumptions about physiology. These dynamic structures may correspond to different tissue types or different organs or they may simply be a useful way of characterising the data. This paper describes a method of automatically extracting factor images and curves from contrast enhanced MRI studies of the brain. This method has been applied to 107 studies carried out on patients with acute stroke. The results show that FADS is able to extract factor curves correlated to arterial and venous signal intensity curves and that the corresponding factor images allow a distinction to be made between areas of the brain with normal and abnormal perfusion. The method is robust and can be applied routinely to dynamic studies of the brain. The constraints described are sufficiently general to be applicable to other dynamic MRI contrast enhanced studies where an increase in contrast concentration produces an increase in signal intensity.

Scaphoid blood flow and acute fracture healing: A dynamic MRI study with enhancement with gadolinium

We have investigated whether assessment of blood flow to the proximal scaphoid can be used to predict nonunion in acute fractures of the scaphoid. We studied 32 fractures of the scaphoid one to two weeks after injury, by dynamic fat-suppressed T1-weighted gradient-echo MRI after the intravenous administration of gadopentetate dimeglumine (0.1 mmol/kg body-weight). Steepest slope values (SSV) and percentage enhancement values (%E) were calculated for the distal and proximal fragments and poles. All the fractures were treated by immobilisation in a cast, and union was assessed by CT at 12 weeks. Nonunion occurred in four fractures (12%), and there was no statistically significant difference between the proximal fragment SSV and %E values for the fractures which united and those with nonunion. The difference between the proximal pole SSV and %E values for the union and nonunion groups reached statistical significance (p < 0.05), but with higher enhancement parameters for the nonunion group. Our results suggest that poor proximal vascularity is not an important determinant of union in fractures of the scaphoid.

Limitations of clinical diagnosis in acute stroke

Trials in acute stroke have recruited on the basis of clinical diagnosis. Using MRI we have shown that clinical diagnosis is more limited than previously appreciated, thus trials may have been underpowered or confounded.

Contrast-reduced imaging of tissue concentration and arterial level (CRITICAL) for assessment of cerebral hemodynamics in acute stroke by magnetic resonance

RATIONALE AND OBJECTIVES To compare cerebral perfusion data obtained by using a low-dose, T1-weighted MRI technique with radionuclide (single positron emission computed tomography [SPECT]) brain imaging and to assess the reproducibility of parametric MRI data (cerebral blood flow [CBF], cerebral blood volume [CBV], and time to peak [TTP]) by applying a previously described nuclear medicine technique to derive quantitative perfusion data. METHODS Single-slice brain and neck images were rapidly acquired during the passage of a small (1/10th of normal dose) bolus of contrast. Parametric images were constructed from the MR data by extracting the bolus transit curve for the brain and the peak arterial input curve from the carotid vessels in the neck. These were compared with SPECT perfusion imaging. Twenty-four patients with acute stroke were studied with both techniques; 13 underwent repeated scanning to assess data reproducibility. RESULTS Relative CBF data were comparable to SPECT data (r = 0.584, P = 0.01). Results were reproducible for relative CBF, CBV, and TTP. The arterial input function was significantly different on the second injection with an average difference of 73.5, suggesting that the signal-concentration relationship had lost linearity with increased contrast load. Absolute quantitative MRI data produced values in the expected range (CBF = 42.6 mL x 100 g(-1) x min(-1)). CONCLUSIONS This technique allows estimation of CBF in the setting of acute stroke with quantitative values in the expected range. Repeated measurements in the same patients showed that this technique provides a reproducible measure of relative CBF, CBV, and TTP.

Scaphoid blood flow and acute fracture healing

We have investigated whether assessment of blood flow to the proximal scaphoid can be used to predict nonunion in acute fractures of the scaphoid. We studied 32 fractures of the scaphoid one to two weeks after injury, by dynamic fat-suppressed T1-weighted gradient-echo MRI after the intravenous administration of gadopentetate dimeglumine (0.1 mmol/kg body-weight). Steepest slope values (SSV) and percentage enhancement values (%E) were calculated for the distal and proximal fragments and poles. All the fractures were treated by immobilisation in a cast, and union was assessed by CT at 12 weeks. Nonunion occurred in four fractures (12%), and there was no statistically significant difference between the proximal fragment SSV and %E values for the fractures which united and those with nonunion. The difference between the proximal pole SSV and %E values for the union and nonunion groups reached statistical significance (p < 0.05), but with higher enhancement parameters for the nonunion group. Our results suggest that poor proximal vascularity is not an important determinant of union in fractures of the scaphoid.

Differences in the diagnostic accuracy of acute stroke clinical subtypes defined by multimodal magnetic resonance imaging

Background: Despite its importance for acute stroke management, little is known about the underlying pathophysiology when patients with acute stroke are classified using clinical methods. Objective: To examine the relation between the magnetic resonance defined stroke subtype and clinical stroke classifications using diffusion weighted imaging (DWI), perfusion weighted imaging (PWI), and angiographic magnetic resonance techniques. Methods: Consecutive patients with clinical syndromes consistent with acute anterior circulation stroke were assessed clinically within six hours of onset and scanned as soon as possible using multimodal magnetic resonance imaging (MRI). Patients were classified clinically into total or partial anterior circulation syndromes using the Oxford classification, or according the severity of the National Institutes of Health stroke scale (NIHSS) (severe > 15; mild/moderate ≤ 15). At day seven, patients were classified by combining clinical course and MRI data as misdiagnosed, misclassified, suffering transient ischaemic attack, infarct with recanalisation, or infarction with persisting occlusion. Patients with occlusion were further divided on the basis of a large diffusion–perfusion mismatch. Results: 84 patients with clinical anterior circulation syndromes were studied. Using the NIHSS, 42 were mild to moderate (0–15) and 42 were severe (> 15). There were 42 with partial anterior circulation syndromes (PACS) and 42 with total anterior circulation syndromes (TACS). Patients with TACS or severe stroke were more likely to have actually suffered a stroke (Fischer’s exact test, p = 0.01), to have a correctly classified stroke (χ2 28.2, p < 0.01), to have persisting occlusion (χ2 30.6, p < 0.01), and to have a large DWI–PWI mismatch (χ2 17.1, p < 0.01). Conclusions: There is more inaccuracy in patients presenting with acute PACS or clinically mild to moderate anterior circulation stroke than in those with TACS or severe acute stroke syndromes. The latter appear more likely to be the targets for acute stroke interventions, as they include a significantly higher proportion of patients with persisting occlusion and diffusion/perfusion mismatch.

Perfusion MRI of infarcted and noninfarcted brain tissue in stroke: a comparison of conventional hemodynamic imaging and factor analysis of dynamic studies.

Martel AL, Allder SJ, Delay GS, et al. Perfusion MRI of infarcted and noninfarcted brain tissue in stroke: A comparison of conventional hemodynamic imaging and factor analysis of dynamic studies. Invest Radiol 2001;36:378–385. rationale and objectives. To investigate the hemodynamics of infarcted and noninfarcted regions of the brain in patients with stroke secondary to a complete middle cerebral artery occlusion. Also, to compare factor analysis, a novel method of analyzing perfusion-weighted images, with more conventional techniques. methods.Twenty-two patients with complete unilateral occlusion of the middle cerebral artery were examined by T1-weighted, contrast-enhanced, perfusion-weighted imaging, diffusion-weighted imaging, and magnetic resonance angiography. Quantitative cerebral blood volume (CBV), cerebral blood flow (CBF), and time-to-peak-intensity (TTP) images were generated. Factor analysis of dynamic studies (FADS) was used to generate “early” and “late” images. The hemodynamic parameters for the infarcted and noninfarcted regions of the occluded territory were compared with those for the brain territory on the nonoccluded side. results.Three regions were shown: (1) Normal tissue on the unaffected side; (2) an infarcted region, which was characterized by reduced CBV, CBF, and early FADS values with increased TTP values; and (3) a noninfarcted region with reduced early FADS and increased late FADS and TTP values compared with the normal region. Cerebral blood volume and CBF values were not reduced significantly in the noninfarcted region. conclusions.The differences in parameters such as TTP, CBV, and CBF are significant, and it is necessary to use more than one parameter when interpreting magnetic resonance imaging perfusion data. Factor analysis of dynamic studies provides additional information to conventional methods of analyzing perfusion data.