Effectiveness and Power of Abdominal Ultrasonography in the Assessment of Crohn's Disease Activity: Comparison with Clinical, Endoscopic, and CT Enterography Findings.

BACKGROUND: Non-invasive methods play an important role in clinical assessment of Crohn's disease. Recent studies have highlighted the effectiveness and reliability of intestinal ultrasonography. We aimed to examine the relationship between intestinal ultrasonography and the clinical, endoscopic, and computed tomography enterography findings, and to assess the activity of Crohn's disease. METHODS: This was a 1-year prospective study involving patients diagnosed with Crohn's Disease. Clinical and endoscopic activity indi- ces, and intestinal ultrasonography and computed tomography enterography findings were evaluated. Intestinal wall thickness, mes- enteric inflammation, lymphadenopathy, and complications were evaluated by intestinal ultrasonograpy and computed tomography enterography, while the superior mesenteric artery flow velocity, resistive index, and Limberg score were assessed by Doppler intestinal ultrasonography. RESULTS: Seventy-nine patients with Crohn's disease were included. A significant correlation was found between intestinal wall thick- ness, mesenteric inflammation, and complications in intestinal ultrasonography and computed tomography enterography (P = .0001). According to the receiver operating curve analysis, the intestinal wall thickness, and mesenteric inflammation were correlated with the Crohn's Disease Activity Index, Harvey-Bradshaw Index, and SES-CD scores (P < .05), and they were very effective in distinguishing active from inactive disease. According to the Crohn's Disease Activity Index and SES-CD scores, Doppler flow velocity of the superior mesenteric artery was significantly higher in the active group than in the inactive group (P < .05). The Limberg score was very consistent with the Crohn's Disease Activity Index, Harvey-Bradshaw Index , and the results of the Simple Endoscopic Score for Crohn's Disease (P < .0001). CONCLUSION: Our study showed that intestinal ultrasonography is an effective and reliable method for assessment of Crohn's disease activity compared to clinical, endoscopic, and CTE findings.

Three-dimensional transesophageal echocardiography vs cardiac magnetic resonance in the assessment of planimetric mitral valve area in rheumatic mitral stenosis.

AIM: Rheumatic heart disease is a common cause of valvular disease, especially in developing countries. Echocardiography is the gold standard investigation modality for cardiac valves. In rheumatic mitral stenosis (MS), three-dimensional transesophageal echocardiography (3D TEE) provides better alignment of the image plane at the mitral tips and more accurate and reproducible planimetric measurement of mitral valve area (MVA). Cardiac magnetic resonance (CMR) is a new method that provides evaluation of cardiac anatomy and function noninvasively. Previous studies showed strong correlation between planimetric MVA measured by two-dimensional transthoracic echocardiography and CMR. We aimed to compare the planimetric MVAs assessed by 3D TEE and CMR in rheumatic MS patients. To best of our knowledge, this is the first study that compares 3D TEE and CMR for the assessment of the planimetric MVA in rheumatic MS. METHODS: We retrospectively evaluated 28 rheumatic MS patients who underwent 3D TEE and ECG-gated CMR. 3D TEE planimetric MVAs were measured manually by multiplanar reconstruction (MPR) method and CMR planimetric MVAs were measured manually on short-axis cine images. Then, 3D TEE and CMR measurements were compared. RESULTS: A total of 28 patients' (mean age 44 ± 12, 82.1% female) planimetric 3D TEE MVAs (1.00 ± 0.20 cm2 ) and CMR MVAs (1.04 ± 0.17 cm2 ) were found to be highly correlated (P < 0.0001, r: 0.744) with Pearson correlation analysis. Bland-Altman analysis showed strong agreement between two techniques. CONCLUSION: For the diagnosis and the follow-up of rheumatic MS, planimetric CMR MVA is an alternative noninvasive method which highly correlates with planimetric 3D TEE MVA.

The advantages of live/real-time three-dimensional echocardiograhy in the assessment of left ventricular myxoma, which causes partial left ventricular outflow tract obstruction.

Myxomas are the most common cardiac primary tumors; however, left ventricular myxomas are extremely rare. We describe a young female patient with a giant left ventricular myxoma causing partial obstruction of the left ventricular outflow tract, who underwent successful surgical resection. Real-time three-dimensional echocardiography yielded incremental value to two-dimensional echocardiography by allowing better assess of the true size, extent, attachment, and morphology of the tumor. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:273-277, 2018.

Assessment of relationships between novel inflammatory markers and presence and severity of preeclampsia: Epicardial fat thickness, pentraxin-3, and neutrophil-to-lymphocyte ratio.

OBJECTIVE: The aim of this study was to evaluate the relation of three new inflammatory markers with presence and severity of preeclampsia and to compare the predictive values of all markers for presence of this setting. METHODS: In this study, a total of 100 consecutive pregnants with a diagnosis of preeclampsia and 40 healthy pregnants between October 2014 and April 2015 were included. Epicardial fat tissue was calculated by two-dimensional transthoracic echocardiography, and pentraxin-3 and neutrophil-to-lymphocyte ratio were measured by using an enzyme-linked immunosorbent assay method and routine blood count analysis, respectively. RESULTS: Epicardial fat thickness (p < 0.001), pentraxin-3 (p < 0.001), and neutrophil-to-lymphocyte ratio (p < 0.001) were found to be significantly increased in the preeclampsia as compared to the healthy pregnants. Furthermore, epicardial fat thickness (p = 0.002), pentraxin-3 (p < 0.001), and neutrophil-to-lymphocyte ratio (p < 0.001) were significantly elevated in the severe preeclampsia compared to mild preeclampsia. In the multivariate analysis, epicardial fat thickness (p = 0.013), pentraxin-3 (p = 0.04), and neutrophil-to-lymphocyte ratio (p < 0.001) were found as significant independent predictors of presence of preeclampsia after adjusting for other risk factors. CONCLUSION: Epicardial fat thickness, neutrophil-to-lymphocyte ratio, and pentraxin-3 are important markers that provide an additional information beyond that provided by conventional methods in predicting presence and severity of preeclampsia.

Assessment of relationship between galectin-3 and ambulatory ECG-based microvolt T-wave alternans in sustained systolic-diastolic hypertension patients.

OBJECTIVES: Galectin-3 is a marker associated with myocardial fibrosis and left ventricular myocardial index (LVMI). Myocardial fibrosis and LVMI have been reported in many studies to be associated with microvolt T-wave alternans (MTWA) positivity. In this study, galectin-3 levels of normotensive individuals and sustained systolic-diastolic hypertensive patients were compared and the association between galectin-3 levels and ambulatory ECG-based MTWA was investigated. METHODS: A total of 184 individuals were included in the study, among whom, 43 were normotensive and 141 had sustained systolic-diastolic hypertension without cardiovascular or chronic renal failure. Galectin-3, MTWA, and LVMI were evaluated in all participants. Galectin-3 levels of hypertensive and normotensive participants were compared. The association between galectin-3, MTWA, LVMI, and estimated glomerular filtration rate (eGFR) was investigated in hypertensive patients. RESULTS: LVMI and galectin-3 levels were higher among hypertensive patients compared with normotensives (94.9±26.8 vs. 76.4±22.9 g/m, 7.325±2.123 vs. 5.233±1.506 ng/ml; P<0.001, P<0.001). Correlation analysis carried out among the hypertensive patients showed that the galectin-3 level was correlated positively to LVMI, age, and MTWA positivity (r=0.396, P<0.001; r=0.358, P<0.001; r=0.361, P<0.001, respectively), whereas it was correlated negatively to eGFR and male sex (r=-0.364, P<0.001; r=-0.280, P=0.001, respectively). Multiple logistic regression analysis indicated that LVMI and galectin-3 showed an independent association with MTWA positivity in hypertensive patients (P=0.003 and 0.005, respectively). CONCLUSION: Increased galectin-3 levels are associated with ambulatory ECG-based MTWA positivity, decreased eGFR, and increased LVMI in hypertensive patients. This association may be used for risk classification in this patient group.

Cardiac Computed Tomography versus Echocardiography in the Assessment of Stenotic Rheumatic Mitral Valve.

PURPOSE: There are different clinical cardiac applications of dual source computed tomography (DSCT). Here, we aimed to compare the DSCT with the transthoracic echocardiography (TTE) for evaluating the Wilkins score and planimetric mitral valve area (MVA) of a rheumatic stenotic mitral valve. MATERIALS AND METHODS: We prospectively evaluated mitral valvular structure and function in 31 patients with known mitral stenosis undergoing electrocardiogram-gated, second-generation DSCT, in our heart center for different indications. Mitral valve was evaluated using Wilkins score, and also, the planimetric MVA was assessed. RESULTS: We found a significant difference between MVAs determined by DSCT (average 1.42 ± 0.44 cm2) and MVAs determined by TTE (average 1.35 ± 0.43 cm2 ; difference 0.07 ± 0.16 cm2; P = 0.018). Linear regression analysis revealed a good correlation between the two techniques (r = 0.934; P < 0.0001). The limits of agreement for DSCT and TTE in the Bland-Altman analysis were ±0.31 cm2 . DSCT using TTE as the reference enabled good discrimination between mild and moderate-to-severe stenosis and had an area under the ROC curve of 0.967 (CI 0.912-1.023; P < 0.0001). Wilkins scores obtained by DSCT (7.51 ± 1.17, range 5-10) and TTE (8.16 ± 1.27, range 6-10) had a moderate correlation (r = 0.686; P < 0.0001). CONCLUSION: We found that planimetric MVA measurements assessed by DSCT were closely correlated with MVA calculations by TTE. The moderate correlation was observed for the Wilkins score.

Assessment of Mean Platelet Volume in Patients with Resistant Hypertension, Controlled Hypertension and Normotensives.

OBJECTIVE: Patients with resistant hypertension are at increased risk for cardiovascular events. Mean platelet volume (MPV) is an accepted biomarker of platelet activation and considered as a risk factor for cardiovascular disease. The aim of this study was to determine whether MPV levels are higher in resistant hypertensive (RHTN) patients than in controlled hypertensive (CHTN) patients and healthy normotensive controls. MATERIALS AND METHODS: 279 consecutive patients were included in this study. Patients were divided into three groups: Resistant hypertension patient group [n=78; mean age 56.8±9.8; 42 males (53.8%)]; controlled hypertension patient group [n=121; mean age 54.1±9.6; 49 males (40.5%)]; and normotensive control group [n=80; mean age 49.8±8.5; 34 males (42.5%)]. Physical examination, laboratory work-up, and 24-hour ambulatory blood pressure measurement (ABPM) were performed in all participants. RESULTS: The mean platelet volume levels were significantly higher in RHTN group than in the CHTN and normotensive groups (p<0.001). In correlation analysis office systolic and diastolic blood pressure was positively correlated with MPV. CONCLUSION: Our study demonstrated that MPV, as an important indicator of platelet activation, was statistically higher in RHTN patients than in CHTN and in normotensive subjects. Elevated MPV levels may help to determine a high risk group for atherosclerosis in RHTN patients.

Assessment of the Relationship Between Serum Vascular Adhesion Protein-1 (VAP-1) and Severity of Calcific Aortic Valve Stenosis.

BACKGROUND: Vascular adhesion protein-1 (VAP-1), a dual-function glycoprotein, is secreted by endothelial cells, adipocytes, and kidney and vascular smooth muscle cells. It has been reported to participate in the development of atherosclerosis as an adhesion molecule and a pro-inflammatory enzyme. Increased VAP-1 levels are related to type 2 diabetes mellitus, atherosclerosis, stroke and chronic renal failure. The study aim was to investigate serum VAP-1 levels in patients with calcific aortic stenosis (AS) and the possible relationship between VAP-1 and severity of calcific AS. METHODS: A total of 168 patients was categorized as having mild (n = 54), moderate (n = 58), or severe (n = 56) AS. Serum VAP-1 levels were measured using an enzyme-linked immunosorbent assay. RESULTS: The mean serum VAP-1 level was significantly higher in patients with AS compared to healthy controls (244.3 ± 50.1 ng/ml versus 149.8 ± 27.5 ng/ml, p <0.001), and in the severe AS group compared to the moderate and mild AS groups (288.3 ± 30.1 ng/ml, 243.1 ± 31.8 ng/ml, and 200.8 ± 43.2 ng/ml, respectively, p <0.001). The VAP-1 level was positively related to the maximum aortic gradient, mean aortic gradient, and maximum aortic jet velocity (r = 0.649, p <0.001; r = 0.660, p <0.001; r = 0.655, p <0.001, respectively) and negatively related to the aortic valve area (r = -0.683, p <0.001). CONCLUSIONS: The present study was the first to demonstrate a significant relationship between increased serum VAP-1 levels and the severity of calcific AS. VAP-1 might be a useful biomarker for the evaluation of AS and the follow up of its severity.

The assessment of relationship between fragmented QRS complex and left ventricular wall motion score index in patients with ST elevation myocardial infarction who underwent primary percutaneous coronary intervention.

OBJECTIVES: Fragmented QRS (fQRS) has been found to be associated with high mortality and arrhythmic events in acute coronary syndromes. Regional systolic function using wall motion score index (WMSI) is an alternative to left ventricular ejection fraction (LVEF) for the assessment of left ventricular systolic function. The aim of this study was to investigate the relation between the presence of fQRS on admission electrocardiogram (ECG) and WMSI in ST elevation myocardial infarction (STEMI) underwent primary coronary intervention (PCI). The in-hospital and long-term prognostic significance of persistent fQRS was also evaluated. METHODS: In this retrospective study, 542 patients with a diagnose of STEMI underwent primary PCI were included. Study patients were divided into two groups according to the presence (n = 153) or absence (n = 389) of a fQRS on admission ECG. RESULTS: WMSI was found to be significantly higher in fQRS(+) group compared to the fQRS(-) group (P < 0.001). In multivariete analysis, WMSI was found to be an independent predictor of fQRS, and fQRS was inversely associated with LVEF. The in-hospital reinfarction (P = 0.003), MACE (P = 0.024), intraaortic balloon pump use (P = 0.014), and advanced heart failure (P < 0.001) were found to be significantly more frequent in the fQRS(+) group. The presence of fQRS on admission was found to be associated with an increase in long-term cardiovascular mortality (P = 0.028), and long-term all-cause mortality (P = 0.022). CONCLUSION: WMSI was significantly related with the presence of the fQRS, which reflects the linking between impairment of regional left ventricular systolic function and the presence of severe myocardial injury in STEMI.

Assessment of the relationship between nondipping phenomenon and microvolt T-wave alternans.

OBJECTIVE: The aim of this cross-sectional study was to evaluate microvolt T-wave alternans (MTWA) as a marker of myocardial electrical instability in normotensive and hypertensive individuals with either nondipper or dipper-type circadian rhythm of blood pressure. MATERIALS AND METHODS: The study group included a total of 181 patients: 118 hypertensive patients and 63 normotensive healthy volunteers [mean age 46 ± 8; 34 men (54%)]. The patients with hypertension were divided into two groups on the basis of their results of 24-h ambulatory blood pressure monitoring: 61 patients with dipper hypertension [mean age 46 ± 6; 32 men (52.5%)] and 57 patients with nondipper hypertension [mean age 48 ± 10; 36 men (63.2%)]. The MTWAs of all patients were analyzed using the time-domain modified moving average method by means of a treadmill exercise stress test. RESULTS: MTWA positivity was statistically significantly different between all groups. Left ventricular mass index, E/E', interventricular septum, posterior wall, 24-h systolic blood pressure and diastolic blood pressure, and night-time systolic blood pressure and diastolic blood pressure were correlated positively with MTWA. Left ventricular mass index and the presence of nondipper hypertension were determined to be independent predictors of MTWA positivity. CONCLUSION: The blunting of the nocturnal decrease in blood pressure was associated with MTWA positivity in hypertensive patients.

Assessment of mean platelet volume and soluble CD40 ligand levels in patients with non-dipper hypertension, dippers and normotensives.

UNLABELLED: Abstract Objective: Patients with a lack of nocturnal decline in blood pressure (BP) are at an increased risk for cardiovascular events. Mean platelet volume (MPV) and soluble CD40 ligand (sCD40L) are accepted biomarkers of platelet activation and considered as a risk factor for cardiovascular disease. The aim of this study was to determine whether MPV and sCD40L levels are higher in non-dipper hypertensive (NDHT) patients than in dipper hypertensive (DHT) patients and healthy controls. METHODS: 124 consecutive patients were included to this study. Patients were divided into three groups: NDHT patient group [n = 43; mean age 51.8 ± 6.6; 31 males (72.1%)]; DHT patient group [n = 41; mean age 50.2 ± 7.3; 22 males (53.7%)]; and normotensive group [n = 40; mean age 49.9 ± 6.7; 22 males (55%)]. Physical examination, laboratory work-up and 24-h ABPM were performed for all participants. RESULTS: The sCD40L and MPV levels were significantly higher in the NDHT group than in the DHT and normotensive groups (p < 0.05). In correlation analysis, MPV, 24-h systolic blood pressure (SBP), 24-h diastolic blood pressure (DBP), night-time SBP and night-time DBP were positively correlated with sCD40L. CONCLUSION: Our study demonstrated that MPV and sCD40L levels were significantly higher in NDHT patients compared to DHT and normotensive patients. sCD40L levels were positively correlated with MPV, 24-h SBP, 24-h DBP, night-time SBP and night-time DBP.

Assessment of sustained effects of levosimendan and dobutamine on left ventricular systolic functions by using novel tissue Doppler derived indices in patients with advanced heart failure.

BACKGROUND: Previous studies comparing levosimendan vs. dobutamine have revealed that levosimendan is better in relieving symptoms. Echocardiographic studies have been done using second measurements immediately following a dobutamine infusion or while it was still being administered. The aim of our study was assessment of sustained effects of 24 h levosimendan and dobutamine infusions on left ventricular systolic functions. METHODS: A total of 61 patients with acutely decompensated heart failure with New York Heart Association (NYHA) class III or IV symptoms were randomized to receive either levosimendan or dobutamine 2:1 in an open label fashion. Before and 5 days after the initiation of infusions, functional class was assessed, N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) levels and left ventricular ejection fraction (LVEF), mitral inflow peak E and A wave velocity, and E/A ratios were measured; using tissue Doppler imaging, isovolumic myocardial acceleration (IVA), peak myocardial velocity during isovolumic contraction (IVV), peak systolic velocity during ejection period (Sa), early (E') and late (A') diastolic velocities, and E'/A' and E/E' ratios were measured. RESULTS: The NYHA class improved in both groups, but improvements were prominent in the levosimendan group. NT-proBNP levels were significantly reduced in the levosimendan group. Improvements in LVEF and diastolic indices were significant in the levosimendan group. Tissue Doppler-derived systolic indices of IVV and IVA increased significantly in the levosimendan group. CONCLUSIONS: Improvements in left ventricular systolic and diastolic functions continue after a levosimendan infusion.

Assessment of the relation between mean platelet volume, non-dipping blood pressure pattern, and left ventricular mass index in sustained hypertension.

BACKGROUND: Elevated mean platelet volume may reflect presence of active large platelets, which lead to fatal or non-fatal cardiovascular events. In recent studies, lack of nocturnal blood pressure fall was presented as an independent predictor of poor prognosis in essential hypertension. The relation of raised MPV with left ventricular hypertrophy has also been reported in hypertension. The aim of this study was to investigate the relation between MPV, non-dipping blood pressure pattern, and left ventricular mass index (LVMI) in sustained hypertension. MATERIAL AND METHODS: A total of 2500 patients, whose ambulatory blood pressure (ABP) records had been evaluated retrospectively between January 2010 and December 2012, were included. Patients were divided into 3 groups according to their ABP values: non-dipper hypertensive (n=289), dipper hypertensive (n=255), and normotensive (n=306). The MPV levels and biochemical analyses were recorded from patient files and, LVMI were automatically calculated using a regression equation. RESULTS: The non-dipper and dipper hypertensive groups had significantly higher MPV levels than normotensives (8.4±1 fL, 8.3±1 fL, and 8.1±0.6 fL, respectively, p<0.001). However, there was no difference among the non-dipper and dipper groups in terms of MPV level (p=0.675). Although LVMI was significantly different between non-dipper, dipper, and normotensive groups (p=0.009), no correlation was found between MPV level and LVMI in dipper and non-dipper hypertensive patients (r=-0.080, p=0.142). There was a weak correlation between MPV level and ambulatory 24-h diastolic and systolic blood pressure (r=0.076, p=0.027, and r=0.073, p=0.033, respectively). CONCLUSIONS: We demonstrated that there was no correlation between MPV level, non-dipping pattern of blood pressure, and LVMI in sustained hypertension.

The assessment of relationship between left ventricular geometry and microvolt T-wave alternans in sustained hypertension.

OBJECTIVE: Left ventricular (LV) hypertrophy (LVH) predicts increased mortality in part due to an elevated incidence of sudden cardiac death in hypertension. The aim of the present study was to investigate the relation of microvolt T-wave alternans (MTWA) with different LV geometric patterns in patient with sustained hypertension. METHODS: This study consisted of 311 consecutive patients with sustained hypertension who were divided into four groups according to LV geometrical patterns. 90 patients were in the normal geometry group (NGG) [mean age 49.6 ± 7.8 years; 60 males (66.7%)], 99 patients were in the concentric remodeling group (CRG) [mean age 50.9 ± 6.6 years; 50 males (50.6%)], 63 patients were in the concentric hypertrophy group (CHG) [mean age 51.6 ± 7.3 years; 32 males (50.7%)] and 58 patients were in the eccentric hypertrophy group (EHG) [mean age 51.6 ± 9.0 years; 30 males (51.7%)]. Physical examination, laboratory work-up, office blood pressure measurement, transthoracic echocardiography and MTWA measurements were performed on all participants. RESULTS: MTWA positivity was significantly higher in EHG and CHG as compared to CRG and NGG (p < 0.001). Left ventricle mass index (LVMI), LV end-diastolic diameter (LVEDD), LV end-systolic diameter (LVESD), interventricular septum diameter (IVSd), posterior wall diameter (PWd) and office systolic blood pressure (SBP) were found to be significantly positively correlated with MTWA (all p-values < 0.05). CONCLUSION: We demonstrated that increased LVMI is associated with an elevated MTWA positivity in sustained hypertensives. Moreover, clinically significant LV geometric patterns including both concentric and eccentric hypertrophy are related with a raised MTWA positivity, which may lead to particular predilection to life-threatening ventricular arrhythmias and sudden cardiac death in sustained hypertension.

Low-dose 18F-FDG PET/CT enterography: improving on CT enterography assessment of patients with Crohn disease.

UNLABELLED: The purpose of this study was to evaluate the diagnostic efficacy of low-dose, combined (18)F-FDG PET/CT enterography (PET/CTE), compared with CT enterography (CTE) alone, in the assessment of patients with Crohn disease. METHODS: Thirteen patients with Crohn disease were prospectively enrolled in this pilot study and underwent abdominal-pelvic (18)F-FDG PET/CTE using neutral oral and intravenous contrast medium. The effective dose from PET/CTE was 17.7 mSv for the first 4 patients and 8.31 mSv for the last 9 patients. Six patients underwent surgical resection of the bowel, and 7 patients underwent colonoscopy with biopsies within 27 d (mean, 12 d) of PET/CTE. PET/CTE and CTE images were each visually assessed for Crohn disease involvement in 54 bowel segments with pathology correlation. Extraintestinal findings were recorded. A CTE severity score, maximum standardized uptake value (SUVmax), SUVmax ratio, simplified endoscopic score, and clinical parameters were correlated with pathology inflammation grade, on a per-patient basis and on a per-bowel-segment basis, using Spearman correlation. RESULTS: In 3 (23.1%) of 13 patients, (18)F-FDG uptake using PET/CTE revealed active inflammation in a bowel segment not evident using CTE (n = 2) or revealed an enterocolic fistula missed with CTE (n = 1). Visual interpretation of both PET/CTE and CTE images detected the presence of disease in all bowel segments with more than mild inflammation (sensitivity, 100%; specificity, 89.7%; positive predictive value, 78.9%; and negative predictive value, 100%). Correlation to inflammation grade per patient was the strongest for the SUVmax ratio (0.735, P = 0.004) and SUVmax (0.67, P = 0.013), as compared with the CTE score (0.62, P = 0.024). Correlation with inflammation per bowel segment was higher for the CTE score (0.79, P < 0.0001) than the SUVmax ratio (0.62, P < 0.0001) or SUVmax (0.48, P < 0.0001). SUVmax correlated strongly with serum C-reactive protein (0.82, P = 0.023), but CTE score did not. CONCLUSION: Low-dose (18)F-FDG PET/CTE, compared with CTE, may improve the detection and grading of active inflammation in patients with Crohn disease. PET/CTE also may reveal clinically significant findings, such as enterocolic fistula, not evident on PET or CTE alone.