Daniel S. Hippe

Sustained Acceleration in Carotid Atherosclerotic Plaque Progression With Intraplaque Hemorrhage: A Long-Term Time Course Study

OBJECTIVES This study sought to determine the immediate and long-term effects of intraplaque hemorrhage (IPH) on plaque progression in the carotid artery. BACKGROUND Previous studies have associated IPH in the carotid artery with more rapid plaque progression. However, the time course and long-term effect remain unknown. Carotid magnetic resonance imaging is a noninvasive imaging technique that has been validated with histology for the accurate in vivo detection of IPH and measurement of plaque burden. METHODS Asymptomatic subjects with 50% to 79% carotid stenosis underwent carotid magnetic resonance imaging at baseline and then serially every 18 months for a total of 54 months. Subjects with IPH present in at least 1 carotid artery at 54 months were selected. Subsequently, presence/absence of IPH and wall volume were determined independently in all time points for both sides. A piece-wise progression curve was fit by using a linear mixed model to compare progression rates described as annualized changes in wall volume between periods defined by their relationship to IPH development. RESULTS From 14 subjects who exhibited IPH at 54 months, 12 arteries were found to have developed IPH during the study period. The progression rates were -20.5 ± 13.1, 20.5 ± 13.6, and 16.5 ± 10.8 mm(3)/year before, during, and after IPH development, respectively. The progression rate during IPH development tended to be higher than the period before (p = 0.080) but comparable to the period after (p = 0.845). The progression rate in the combined period during/after IPH development was 18.3 ± 6.5 mm(3)/year, which indicated significant progression (p = 0.008 compared with a slope of 0) and was higher than the period before IPH development (p = 0.018). No coincident ischemic events were noted for new IPH. CONCLUSIONS The development of IPH posed an immediate and long-term promoting effect on plaque progression. IPH seems to alter the biology and natural history of carotid atherosclerosis. Early identification of patients with IPH may prove invaluable in optimizing management to minimize future sequelae.

Multicontrast High-Resolution Vessel Wall Magnetic Resonance Imaging and Its Value in Differentiating Intracranial Vasculopathic Processes

Background and Purpose— Although studies have attempted to differentiate intracranial vascular disease using vessel wall magnetic resonance imaging (VWI), none have incorporated multicontrast imaging. This study uses T1- and T2-weighted VWI to differentiate intracranial vasculopathies. Methods— We retrospectively reviewed patients with clinically defined intracranial vasculopathies causing luminal stenosis/irregularity who underwent VWI studies. Two blinded experts evaluated T1 precontrast and postcontrast and T2-weighted VWI characteristics, including the pattern of wall thickening; presence, pattern, and intensity of postcontrast enhancement; and T2 signal characteristics. Results— Twenty-one cases of atherosclerosis (intracranial atherosclerotic disease [ICAD]), 4 of reversible cerebral vasoconstriction syndrome, and 4 of vasculitis were identified, with a total of 118 stenotic lesions (81 ICAD, 22 reversible cerebral vasoconstriction syndrome, and 15 vasculitic lesions). There was substantial to excellent inter-reader agreement for the assessment of lesional T2 hyperintensity (&kgr;=0.80), pattern of wall thickening (&kgr;=0.87), presence (&kgr;=0.90), pattern (&kgr;=0.73), and intensity (&kgr;=0.77) of enhancement. ICAD lesions were significantly more likely to have eccentric wall involvement (90.1%) than reversible cerebral vasoconstriction syndrome (8.2%; P<0.001) and vasculitic lesions (6.7%; P<0.001) and were also more likely to have T2 hyperintensity present than the other 2 vasculopathies (79% versus 0%; P<0.001). There were also significant differences in the presence, intensity, and pattern of enhancement between all lesion types. Combining T1 and T2 VWI increased the sensitivity of VWI in differentiating ICAD from other vasculopathies from 90.1% to 96.3%. Conclusions— Multicontrast VWI can be a complementary tool for intracranial vasculopathy differentiation, which often leads to more invasive workups when reversible cerebral vasoconstriction syndrome and vasculitis are in the differential diagnosis.

Simultaneous noncontrast angiography and intraPlaque hemorrhage (SNAP) imaging for carotid atherosclerotic disease evaluation

A simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) MR imaging technique is proposed to detect both luminal stenosis and hemorrhage in atherosclerosis patients in a single scan. Thirteen patients with diagnosed carotid atherosclerotic plaque were admitted after informed consent. All scans were performed on a 3T MR imaging system with SNAP, 2D time‐of‐flight and magnetization‐prepared 3D rapid acquisition gradient echo sequences. The SNAP sequence utilized a phase sensitive acquisition, and was designed to provide positive signals corresponding to intraplaque hemorrhage and negative signals corresponding to lumen. SNAP images were compared to time‐of‐flight images to evaluate lumen size measurements using linear mixed models and the intraclass correlation coefficient. Intraplaque hemorrhage identification accuracy was evaluated by comparing to magnetization‐prepared 3D rapid acquisition gradient echo images using Cohens Kappa. Diagnostic quality SNAP images were generated from all subjects. Quantitatively, the lumen size measurements by SNAP were strongly correlated (intraclass correlation coefficient = 0.96, P < 0.001) with those measured by time‐of‐flight. For intraplaque hemorrhage detection, strong agreement (κ = 0.82, P < 0.001) was also identified between SNAP and magnetization‐prepared 3D rapid acquisition gradient echo images. In conclusion, a SNAP imaging technique was proposed and shows great promise for imaging both lumen size and carotid intraplaque hemorrhage with a single scan. Magn Reson Med, 2013.

Safety and Efficacy of Drug-eluting Bead Chemoembolization for Hepatocellular Carcinoma: Comparison of Small-versus Medium-size Particles

PURPOSE To compare safety and imaging response with 100-300 μm and 300-500 μm doxorubicin drug-eluting bead (DEBs) to determine optimal particle size for chemoembolization of hepatocellular carcinoma (HCC). MATERIALS AND METHODS DEB chemoembolization using 100-300 μm (n = 39) or 300-500 μm (n = 22) LC beads loaded with 50 mg of doxorubicin was performed in 61 patients with HCC. Patient age, sex, etiology of liver disease, degree of underlying liver disease, tumor burden, and performance status were similar between the groups. All treatments were performed in a single session and represented the patients first treatment. Toxicities and imaging response in a single index tumor were analyzed using World Health Organization (WHO) and European Association for the Study of the Liver (EASL) criteria. RESULTS There was a significantly lower incidence of postembolization syndrome and fatigue after treatment in the 100-300 μm group (8% and 36%) versus the 300-500 μm group (40% and 70%) (100-300 μm group, P = .011; 300-500 μm group, P = .025). Mean change in tumor size was similar between the two groups based on WHO and EASL criteria and similar rates of objective response, but there was a trend toward a higher incidence of EASL complete response with 100-300 μm beads versus 300-500 μm beads (59% vs 36%; P = .114). CONCLUSIONS In DEB chemoembolization for treatment of HCC, 100-300 μm doxorubicin DEBs are favored over 300-500 μm doxorubicin DEBs because of lower rates of toxicity after treatment and a trend toward more complete imaging response at initial follow-up.

The association of lesion eccentricity with plaque morphology and components in the superficial femoral artery: a high-spatial-resolution, multi-contrast weighted CMR study

BackgroundAtherosclerotic plaque morphology and components are predictors of subsequent cardiovascular events. However, associations of plaque eccentricity with plaque morphology and plaque composition are unclear. This study investigated associations of plaque eccentricity with plaque components and morphology in the proximal superficial femoral artery using cardiovascular magnetic resonance (CMR).MethodsTwenty-eight subjects with an ankle-brachial index less than 1.00 were examined with 1.5T high-spatial-resolution, multi-contrast weighted CMR. One hundred and eighty diseased locations of the proximal superficial femoral artery (about 40 mm) were analyzed. The eccentric lesion was defined as [(Maximum wall thickness- Minimum wall thickness)/Maximum wall thickness] ≥ 0.5. The arterial morphology and plaque components were measured using semi-automatic image analysis software.ResultsOne hundred and fifteen locations were identified as eccentric lesions and sixty-five as concentric lesions. The eccentric lesions had larger wall but similar lumen areas, larger mean and maximum wall thicknesses, and more calcification and lipid rich necrotic core, compared to concentric lesions. For lesions with the same lumen area, the degree of eccentricity was associated with an increased wall area. Eccentricity (dichotomous as eccentric or concentric) was independently correlated with the prevalence of calcification (odds ratio 3.78, 95% CI 1.47-9.70) after adjustment for atherosclerotic risk factors and wall area.ConclusionsPlaque eccentricity is associated with preserved lumen size and advanced plaque features such as larger plaque burden, more lipid content, and increased calcification in the superficial femoral artery.

Adventitial Perfusion and Intraplaque Hemorrhage: A Dynamic Contrast-Enhanced MRI Study in the Carotid Artery

Background and Purpose— Autopsy studies have suggested a relationship between intraplaque hemorrhage (IPH) and vasa vasorum, which arise primarily from the adventitia. Adventitial vasa vasorum can be characterized in the carotid arteries by estimating perfusion parameters via dynamic contrast-enhanced MRI. The purpose of this investigation was to use dynamic contrast-enhanced MRI to test in vivo in a clinical population whether adventitial perfusion, indicative of vasa vasorum microstructure, is associated with IPH. Methods— Symptomatic patients with carotid plaque ipsilateral to the ischemic event underwent bilateral carotid artery MRI examination, which included multicontrast sequences for detecting IPH and a dynamic contrast-enhanced MRI sequence for characterizing adventitial perfusion. Kinetic modeling of the dynamic contrast-enhanced MRI time series was performed to estimate adventitial vp (fractional plasma volume, reflecting local blood supply) and Ktrans (transfer constant, reflecting vessel surface area, and permeability). Results— From the 27 patients (22 men; 69±10 years of age) recruited, adventitial perfusion parameters were obtained in 50 arteries. The presence of IPH was associated with a significantly higher value in adventitial Ktrans (0.142±0.042 vs 0.112±0.029 min−1; P<0.001) but not in vp (0.163±0.064 vs 0.149±0.062; P=0.338). This relationship remained after adjusting for symptomatic status, degree of stenosis, and other confounding factors. Conclusions— This study demonstrated an independent pathophysiological link between the adventitia and IPH and related it to the microstructure of adventitial vasa vasorum. Adventitial perfusion imaging may be useful in studying plaque pathogenesis, but further examination through prospective studies is needed.

Predictors of Functional Outcome after Emergency Carotid Artery Stenting and Intra-Arterial Thrombolysis for Treatment of Acute Stroke Associated with Obstruction of the Proximal Internal Carotid Artery and Tandem Downstream Occlusion

BACKGROUND AND PURPOSE: Patients who develop severe stroke symptoms due to acute internal carotid artery occlusion eventually in combination with a thromboembolic obstruction of the middle cerebral artery incur a major risk of developing extensive MCA infarction with a poor outcome. The purpose of this study was to evaluate the outcome for patients with tandem occlusions in the MCA and/or distal ICA, retrospectively, who had undergone stent implantation in the proximal segment of the ICA in addition to intra-arterial thrombolysis. MATERIALS AND METHODS: Thirty-five patients with tandem occlusions of the MCA and/or distal ICA and acute occlusion of the proximal ICA underwent stent implantation for the proximal ICA occlusion and IAT for the tandem occlusion. Clinical outcome measures were assessed on admission and at discharge by using the National Institutes of Health Stroke Scale as well as 3 months after treatment by using the modified Rankin Scale. RESULTS: The median NIHSS score on admission was 12 (range, 6–22). All patients had patent flow into the M1 and ICA after carotid artery stent placement and IAT. After the procedure, 19 patients (54.3%) were TICI grade III; 7 (20.0%), TICI grade IIb; and 9 (25.7%), TICI grade IIa. Symptomatic intracerebral hemorrhage occurred in 1 patient (2.9%). The overall mortality rate was 11.4% (4/35). At 3-month follow-up, the median NIHSS score was 4 (range, 1–17). NIHSS score at admission and TICI grade were all found to be independently associated with an unfavorable outcome at 3 months. CONCLUSIONS: Initial stroke severity, degree of successful revascularization, and the side of ischemia were found to independently predict the functional outcome at 3 months after treatment.

Subclinical Carotid Atherosclerosis: Short-term Natural History of Lipid-rich Necrotic Core—A Multicenter Study with MR Imaging

PURPOSE To use magnetic resonance (MR) imaging to examine the short-term (6 months) natural history of the lipid-rich necrotic core (LRNC) in carotid artery plaques by examining the placebo group of a multicenter clinical trial. MATERIALS AND METHODS Study procedures and consent forms were approved by the institutional review board for this HIPAA-compliant study. Written informed consent was obtained for all enrolled subjects. Subjects in the placebo group of a multicenter clinical trial who showed LRNC at screening MR imaging had a follow-up MR imaging examination after 6 months. Lumen and wall volumes and LRNC volume and percentage were measured on images from both examinations by readers who were blinded to the time sequence. Plaque progression was calculated as annualized change in common coverage by using the carotid artery bifurcation as a landmark. Associations of clinical and imaging variables with LRNC progression were examined by using linear regression analysis. RESULTS Fifty-nine of 73 (81%) subjects completed the study, with a mean interval ± standard deviation of 6.9 months ± 1.0. The mean progression rates per year ± standard deviation of LRNC volume and percentage were -5.2 mm(3) ± 34.3 (P = .249) and -1.74% ± 6.27% (P = .038), respectively. Of the clinical and imaging variables examined, presence of intraplaque hemorrhage (IPH) was significantly associated with LRNC progression (P = .001). Plaques with IPH had increased LRNC volume per year (62.9 mm(3) ± 46.2 vs -8.8 mm(3) ± 29.9, P < .001) and percentage per year (3.67% ± 1.85% vs -2.03% ± 6.30%, P = .126) compared with those without IPH. Spearman correlation analysis showed that change in LRNC positively correlated with change in wall volume (ρ = 0.60, P < .001), but not with change in lumen volume (ρ = -0.17, P = .201). CONCLUSION Serial MR imaging of the carotid artery allowed observation of changes in LRNC over a short follow-up period and demonstrated the complexity of plaque progression patterns related to tissue composition. LRNC progression may be influenced not only by clinical characteristics, but also and to a large extent by plaque characteristics such as IPH.

Screening MRI in Women With a Personal History of Breast Cancer

BACKGROUND Screening MRI is recommended for individuals at high risk for breast cancer, based on genetic risk or family history (GFH); however, there is insufficient evidence to support screening MRI for women with a personal history (PH) of breast cancer. We compared screening MRI performance in women with PH vs GFH of breast cancer. METHODS We analyzed case-series registry data, collected at time of MRI and at 12-month follow-up, from our regional Clinical Oncology Data Integration project. MRI performance was compared in women with PH with those with GFH. Chi-square testing was used to identify associations between age, prior history of MRI, and clinical indication with MRI performance; logistic regression was used to determine the combined contribution of these variables in predicting risk of a false-positive exam. All statistical tests were two-sided. RESULTS Of 1521 women who underwent screening MRI from July 2004 to November 2011, 915 had PH and 606 had GFH of breast cancer. Overall, MRI sensitivity was 79.4% for all cancers and 88.5% for invasive cancers. False-positive exams were lower in the PH vs GFH groups (12.3% vs 21.6%, P < .001), specificity was higher (94.0% vs 86.0%, P < .001), and sensitivity and cancer detection rate were not statistically different (P > .99). Age (P < .001), prior MRI (P < .001), and clinical indication (P < .001) were individually associated with initial false-positive rate; age and prior MRI remained statistically significant in multivariable modeling (P = .001 and P < .001, respectively). CONCLUSION MRI performance is superior in women with PH compared with women with GFH. Screening MRI warrants consideration as an adjunct to mammography in women with a PH of breast cancer.

Association of carotid atherosclerotic plaque features with acute ischemic stroke: A magnetic resonance imaging study

BACKGROUND AND PURPOSE It remains unclear whether direct vessel wall imaging can identify carotid high-risk lesions in symptomatic subjects and whether carotid plaque characteristics are more effective indicators for cerebral infarct severity than stenosis. This study sought to determine the associations of carotid plaque characteristics by MR imaging with stenosis and acute cerebral infarct (ACI) sizes on diffusion weighted imaging (DWI). MATERIALS AND METHODS One hundred and fourteen symptomatic patients underwent carotid and brain MRI. ACI volume was determined from symptomatic internal carotid artery territory on DWI images. Ipsilateral carotid plaque morphological and compositional characteristics, and stenosis were also determined. The relationships between carotid plaque characteristics, stenosis and ACIs size were then evaluated. RESULTS In carotid arteries with 30-49% stenosis, 86.7% and 26.7% were found to have lipid-rich necrotic core (LRNC) and intraplaque hemorrhage, respectively. Furthermore, 45.8% of carotid arteries with 0-29% stenosis developed LRNCs. Carotid morphological measurements, such as % wall volume, and the LRNC size were significantly associated with ipsilateral ACIs volume before and after adjustment for significant demographic factors (age and LDL) or stenosis in patients with carotid plaque (all p<0.05). CONCLUSIONS A substantial number of high-risk plaques characterized by vessel wall imaging exist in carotid arteries with lower grade stenosis. In addition, carotid plaque characteristics, particularly the % wall volume and LRNC size, are independently associated with cerebral infarction as measured by DWI lesions. Our findings indicate that characterizing atherosclerotic plaque by MR vessel wall imaging might be useful for stratification of plaque risk and infarction severity.