Peter Olson

Characterization of Signal Properties in Atherosclerotic Plaque Components by Intravascular MRI

Magnetic resonance imaging (MRI) is capable of distinguishing between atherosclerotic plaque components solely on the basis of biochemical differences. However, to date, the majority of plaque characterization has been performed by using high-field strength units or special coils, which are not clinically applicable. Thus, the purpose of the present study was to evaluate MRI properties in histologically verified plaque components in excised human carotid endarterectomy specimens with the use of a 5F catheter-based imaging coil, standard acquisition software, and a clinical scanner operating at 0.5 T. Human carotid endarterectomy specimens from 17 patients were imaged at 37 degrees C by use of an opposed solenoid intravascular radiofrequency coil integrated into a 5F double-lumen catheter interfaced to a 0.5-T General Electric interventional scanner. Cross-sectional intravascular MRI (156x250 microm in-plane resolution) that used different imaging parameters permitted the calculation of absolute T1and T2, the magnetization transfer contrast ratio, the magnitude of regional signal loss associated with an inversion recovery sequence (inversion ratio), and regional signal loss in gradient echo (gradient echo-to-spin echo ratio) in plaque components. Histological staining included hematoxylin and eosin, Massons trichrome, Kossa, oil red O, and Gomoris iron stain. X-ray micrographs were also used to identify regions of calcium. Seven plaque components were evaluated: fibrous cap, smooth muscle cells, organizing thrombus, fresh thrombus, lipid, edema, and calcium. The magnetization transfer contrast ratio was significantly less in the fibrous cap (0.62+/-13) than in all other components (P<0.05) The inversion ratio was greater in lipid (0.91+/-0.09) than all other components (P<0.05). Calcium was best distinguished by using the gradient echo-to-spin echo ratio, which was lower in calcium (0.36+/-0.2) than in all plaque components, except for the organizing thrombus (P<0.04). Absolute T1 (range 300+/-140 ms for lipid to 630+/-321 ms for calcium) and T2 (range 40+/-12 ms for fresh thrombus to 59+/-21 ms for smooth muscle cells) were not significantly different between groups. In vitro intravascular MRI with catheter-based coils and standard software permits sufficient spatial resolution to visualize major plaque components. Pulse sequences that take advantage of differences in biochemical structure of individual plaque components show quantitative differences in signal properties between fibrous cap, lipid, and calcium. Therefore, catheter-based imaging coils may have the potential to identify and characterize those intraplaque components associated with plaque stability by use of existing whole-body scanners.

Endoglin (CD105) and Vascular Endothelial Growth Factor as Prognostic Markers in Prostatic Adenocarcinoma

We studied endoglin and vascular endothelial growth factor (VEGF) expression as prognostic markers in prostatic adenocarcinoma in 50 radical prostatectomy specimens. Cases were further categorized by Gleason score as follows: 8 to 10, 9 cases; 7(4 + 3), 9 cases; 7 (3 + 4), 14 cases; 6, 13 cases; and 4 or 5, 5 cases. All cases were immunostained for endoglin, CD31, and VEGF. Positively stained microvessels were counted in densely vascular foci in a x 400 field. VEGF staining intensity was scored on a 2-tiered scale. Results were correlated with survival and other parameters. Endoglin demonstrated significantly more microvessels than did CD31 (mean +/- SD, 37 +/- 15 vs 22 +/- 17; P < .001). VEGF expression was low in 21 cases (42%) and high in 29 (58%). Endoglin correlated positively with Gleason score, lymph node metastases, tumor stage, and preoperative prostate-specific antigen level (P < .05) but not with CD31. VEGF correlated significantly with angiolymphatic invasion and Gleason score (P < .05). A high endoglin microvessel count and VEGF expression correlated with shorter survival. Endoglin is a more specific and sensitive marker for tumor angiogenesis than CD31 and may serve as a prognostic marker for prostatic adenocarcinoma.

Sentinel lymph node biopsy after neoadjuvant chemotherapy for breast cancer

BACKGROUND Sentinel lymph node biopsy (SLNB) is a developing alternative to axillary dissection and may prove to be accurate in the detection of micrometastases in lymph nodes of breast cancer patients. Limited studies exist in the use of SLNB after neoadjuvant therapy. This study was undertaken to determine the accuracy of SLNB after neoadjuvant chemotherapy. METHODS Thirty-one patients with stage I or II breast cancer underwent SLNB after neoadjuvant chemotherapy. RESULTS Lymphatic mapping was performed by radioisotope, blue dye, or both techniques. Sentinel nodes (SN) were identified in 29 patients (93.5%). The SN was positive in 11 patients (38.0%), and was the only positive node in 5 patients (45.5%). There were no false negative SN by hematoxyin and eosin stain or immunohistochemistry (IHC) studies. CONCLUSIONS Sentinel node identification rate is similar to that in nonneoadjuvant studies. The sentinel node accurately predicted metastatic disease in the axilla. IHC studies failed to detect any additional micrometastases. This diagnostic technique may provide treatment guidance for patients after neoadjuvant therapy.

Microtubule-Associated Protein-2: A New Sensitive and Specific Marker for Pulmonary Carcinoid Tumor and Small Cell Carcinoma

Microtubule-associated proteins (MAPs) are a major component of cytoskeleton family proteins associated with microtubule assembly. MAP-2 has been shown to be specifically expressed in neuronally differentiated cells. Pulmonary neuroendocrine carcinomas such as carcinoid tumors and small cell carcinomas are derived from neuroendocrine cells. We hypothesize that neuroendocrine cells may also express MAP-2, and therefore, MAP-2 may be used as a marker for pulmonary carcinomas of neuroendocrine differentiation. To investigate the utility of using MAP-2 expression to separate pulmonary neuroendocrine from non-neuroendocrine tumors, we examined the expression of MAP-2 immunohistochemically in 100 cases of pulmonary carcinomas. The immunoperoxidase method with antigen retrieval was used to characterize the expression of MAP-2, chromogranin, synaptophysin, and neuron-specific enolase in 25 small cell carcinomas, 25 carcinoid tumors, 25 adenocarcinomas, and 25 squamous cell carcinomas. All tumors were lung primaries. All 25 cases of carcinoid tumors (100%) as well as 23 of 25 cases (92%) of small cell carcinomas were positive for MAP-2. Four of 25 cases (16%) of adenocarcinomas were positive for MAP-2 and synaptophysin. Among the 25 squamous carcinomas, 4 cases (16%) were positive for MAP-2, 2 cases (8%) were positive for synaptophysin, 11 cases (44%) were positive for neuron-specific enolase, and none was positive for chromogranin. In conclusion, MAP-2 is a new sensitive and specific marker for the pulmonary tumors of neuroendocrine differentiation. We recommend that MAP-2 be added to immunohistochemical panels to separate non-neuroendocrine from neuroendocrine lung tumors.

Ex vivo cardiovascular magnetic resonance measurements of right and left ventricular mass compared with direct mass measurement in excised hearts after transplantation: a first human SSFP comparison

BackgroundCMR is considered the `gold standard’ for non-invasive LV and RV mass quantitation. This information is solely based on gradient-recalled echo (GRE) sequences while contrast dependent on intrinsic T1/T2 characteristics potentially offers superior image contrast between blood and myocardium. This study aims, for the first time in humans, to validate the SSFP approach using explanted hearts obtained from heart transplant recipients. Our objective is establish the correlation between and to validate steady-state free precession (SSFP) derived LV and RV mass vs. autopsy mass of hearts from cardiac transplants patients.MethodsOver three-years, 58 explanted cardiomyopathy hearts were obtained immediately upon orthotopic heart transplantation from the OR. They were quickly cleaned, prepared and suspended in a saline-filled container and scanned ex vivo via SSFP-SA slices to define LV/RV mass. Using an automatic thresholding program, segmentation was achieved in combination with manual trimming (ATMT) of extraneous tissue incorporating 3D cardiac modeling performed by independent and blinded readers. The explanted hearts were then dissected with the ventricles surgically separated at the interventricular septum. Weights of the total heart not excluding papillary and trabecular myocardium, LV and RV were measured via high-fidelity scale. Linear regression and Bland-Altman plots were used to analyze the data. The intra-class correlation coefficient was used to assess intra-observer reliability.ResultsOf the total of 58 explanted hearts, 3 (6%) were excluded due to poor image quality leaving 55 patients (94%) for the final analysis. Significant positive correlations were found between total 3D CMR mass (450 ± 111 g) and total pathology mass (445 ± 116 g; r = 0.99, p < 0.001) as well as 3D CMR measured LV mass (301 ± 93 g) and the pathology measured LV mass (313 ± 96 g; r = 0.95, p < 0.001). Strong positive correlations were demonstrated between the 3D CMR measured RV mass (149 ± 46 g) and the pathology measured RV mass (128 ± 40 g; r = 0.76, p < 0.001). The mean bias between 3D-CMR and pathology measures for total mass, LV mass and RV mass were: 3.0 g, -16 g and 19 g, respectively.ConclusionsSSFP-CMR accurately determines total myocardial, LV and RV mass as compared to pathology weighed explanted hearts despite variable surgical removal of instrumentation (left and right ventricular assist devices, AICD and often apical core removals). Thus, this becomes the first-ever human CMR confirmation for SSFP now validating the distinction of `gold standard’.

Role of pulsatile perfusion with tissue plasminogen activator in deceased donor kidneys with extensive glomerular thrombosis.

BACKGROUND Pulsatile perfusion (PP) improves delayed graft function, whereas tissue plasminogen activator (tPA) lyses thrombi. We studied the role of PP with tPA containing perfusate in deceased donor kidneys (DDK) with 50% thrombosed glomeruli. METHODS Fourteen DDK with extensive glomerular thrombi on biopsies were preserved using PP with histidine-tryptophan-ketoglutarate solution containing tPA. Wedge biopsies were repeated after PP. RESULTS Causes of donor death included closed head trauma in 8, anoxia in 2, and stroke in 4. Donors who averaged 33.3 years old displayed a final 24-hour urine volume of 1933 mL, a terminal serum creatinine level of 1.8 mg/dL, a blood urea nitrogen of 20 mg/dL, and a platelet count of 128,000/microL. The initial flow of 47 mL improved to 111 mL/min after 16.17 hours of perfusion. Resistive indices (RI) decreased from 0.69 to 0.26 at 4.2 degrees C. Biopsy specimens after PP showed a reduction in glomerular thrombi from 50% to 23%. Recipients averaged 54.9 years old. Cold ischemia time averaged 35.5 hours. One patient displayed primary allograft nonfunction, 3 required transient dialysis, and 10 showed prompt allograft function. Recipient follow-up averaged 12 months, with serum creatinine levels of 4.3 mg/dL at 1 week, 2.0 mg/dL at 1 month, and 1.6 mg/dL at last follow-up. CONCLUSIONS Renal allografts with extensive glomerular thrombosis improved their biopsy appearance following PP with tPA. Improvement in PP parameters allowed successful transplantation of such kidneys that otherwise would have been discarded. PP with tPA appears to be beneficial for kidneys with extensive glomerular thrombosis.

Significance of microvascular thrombosis in renal allografts: role of ex vivo thrombolytic therapy

Abstract:  Background:  Microvascular thrombosis is an uncommon pathologic finding in cadaveric kidneys. It is associated with disseminated intravascular coagulation most frequently associated with head injuries and massive blood transfusions. The high rate of non‐function published in the literature portends an ominous significance for transplanted organs, which have been discarded by many transplant centers.

Mid wall fibrosis on CMR with late gadolinium enhancement may predict prognosis for LVAD and transplantation risk in patients with newly diagnosed dilated cardiomyopathy—preliminary observations from a high-volume transplant centre

Patients with newly diagnosed dilated cardiomyopathy (DCM) and advanced heart failure have a very high morbidity and mortality with an unpredictable clinical course. We investigated the role of cardiovascular magnetic resonance (CMR) imaging using late gadolinium enhancement (LGE) in this cohort of high‐risk patients. We hypothesized that LGE has high prognostic value in primary DCM patients referred for possible transplantation/left ventricular assist device (LVAD) consideration.BACKGROUND Patients with newly diagnosed dilated cardiomyopathy (DCM) and advanced heart failure have a very high morbidity and mortality with an unpredictable clinical course. We investigated the role of cardiovascular magnetic resonance (CMR) imaging using late gadolinium enhancement (LGE) in this cohort of high-risk patients. We hypothesized that LGE has high prognostic value in primary DCM patients referred for possible transplantation/left ventricular assist device (LVAD) consideration. METHODS Over 49 consecutive months, 61 consecutives DCM patients were referred for standard CMR(1.5T, GE) to interrogate the LV pattern, distribution, and extent of LGE (MultiHance, Princeton, NJ). Inclusion criteria for a primary non-ischaemic DCM and EF <45% were met in 31 patients. DCM patients were categorized into: (i) presence of midwall LV stripe (+Stripe) and (ii) absence of midwall stripe (-Stripe) groups. Primary outcome was defined by the composite of death, need for LV assist device (LVAD), and urgent orthotopic cardiac transplantation (Tx) during a 12-month follow-up period. Kaplan-Meier survival analysis was conducted grouping patients by +Stripe and -Stripe. RESULTS There were no differences between groups for demographics, blood pressure, labs, baseline LVEF, NYHA class, or invasive haemodynamics. There were 18 patients (58%) with +Stripe. Nine events occurred: seven patients required urgent Tx and/or LVAD implantation and two patients died. The +Stripe categorization strongly predicted the need for LVAD, urgent Tx surgery, and death (log-rank = 9, P = 0.002). All the events occurred in the +Stripe patients with no MACE experienced in the -Stripe group. The -Stripe group experienced marked signs of improvement in LVEF (P = 0.01) at follow-up. LVEDD was predictive of need for LVAD/Tx and death by univariate analysis. Otherwise, no common clinical metric such as LVEF, LVEDV, RVEF, RVEDV, or any invasive haemodynamic parameter predicted MACE. CONCLUSIONS The presence of +Stripe on CMR is strongly predictive of LVAD, transplant need, and death during a 12-month follow-up period in DCM patients in this proof of concept study. All -Stripe patients survived without experiencing any events. Incorporating CMR imaging into routine clinical practice may have prognostic value in DCM patients; indicating conservative management in low-risk patients while expectantly managing high-risk patients.

Cardiac Sarcoidosis or Giant Cell Myocarditis? On Treatment Improvement of Fulminant Myocarditis as Demonstrated by Cardiovascular Magnetic Resonance Imaging

Giant cell myocarditis, but not cardiac sarcoidosis, is known to cause fulminant myocarditis resulting in severe heart failure. However, giant cell myocarditis and cardiac sarcoidosis are pathologically similar, and attempts at pathological differentiation between the two remain difficult. We are presenting a case of fulminant myocarditis that has pathological features suggestive of cardiac sarcoidosis, but clinically mimicking giant cell myocarditis. This patient was treated with cyclosporine and prednisone and recovered well. This case we believe challenges our current understanding of these intertwined conditions. By obtaining a sense of severity of cardiac involvement via delayed hyperenhancement of cardiac magnetic resonance imaging, we were more inclined to treat this patient as giant cell myocarditis with cyclosporine. This resulted in excellent improvement of patients cardiac function as shown by delayed hyperenhancement images, early perfusion images, and SSFP videos.

The evaluation of right and left ventricular morphology by CMR with comparison to recipient heart after heart transplant: a surgical perspective

CMR is considered the ‘gold standard’ for non-invasive LV and RV mass quantitation. To our knowledge, this information is soley based on animal and phantom data never having been prospectively or retrospectively validated in humans, undermining its credibility. This issue is particularly important for the RV having complex geometry ill suited for mathematical modeling, placing increased importance on accurate mass quantitation. The surest way to validate the accuracy and thus the true gold standard of CMR derived mass is through autopsy but obviously is not feasible