Hossam M. Sherif

Simplified Quantification of Myocardial Flow Reserve with flurpiridaz F 18: Validation with Microspheres in a Pig Model

The novel PET flow tracer flurpiridaz F 18 shows high myocardial extraction and slow washout. flurpiridaz F 18 PET data analysis with tracer kinetic modeling provides accurate absolute myocardial blood flow (MBF) measurements but requires in-scanner injection and complex processing. We evaluated the hypothesis that myocardial retention and standardized uptake values (SUVs) based on late uptake provide accurate estimates of myocardial flow reserve (MFR) and, thus, might allow simplified quantification after tracer injection outside the scanner. Methods: Nine pigs had dynamic PET scans after repeated injections of flurpiridaz F 18 at rest and combined adenosine and dobutamine stress. flurpiridaz F 18 PET with a 3-compartment model and coinjected radioactive microspheres were used to delineate MBF. These quantitative measurements were compared with myocardial retention (%/min) and SUV of flurpiridaz F 18 after summing data over 5–10, 5–12, 5–15, 10–15, and 10–20 min after tracer injection. Results: MBF ranged from 0.5 to 2.8 mL/min/g. There was a good correlation between both flurpiridaz F 18 retention and SUVs from 5 to 12 min after injection and MBF measured using 3-compartment model– or microsphere-derived MBF (r = 0.73, P < 0.05, and r = 0.68, P < 0.05, respectively, for retention; r = 0.88, P < 0.001, and r = 0.92, P < 0.001, respectively, for SUV). At later time points, retention and SUV underestimated stress microsphere flow (at 10–20 min: r = 0.41, P = not significant, and r = 0.46, P = not significant, respectively, for retention; r = 0.41, P = not significant, and r = 0.65, P < 0.05, respectively, for SUV). When measured 5–12 min after injection, there was a close agreement between MFR measured with either flurpiridaz F 18 retention or SUV and MFR measured using microspheres (mean difference, −0.08 ± 0.36 and −0.18 ± 0.25, respectively). Conclusion: Myocardial retention and SUVs of the 18F-labeled flow tracer flurpiridaz F 18 accurately reflect the MFR. These simplified analysis methods may facilitate the combination of quantitative assessment of perfusion reserve and rapid clinical imaging protocols.

Evaluation of a Novel 18 F-Labeled Positron-Emission Tomography Perfusion Tracer for the Assessment of Myocardial Infarct Size in Rats

Background—The goal of this study was to evaluate a new 18F-labeled positron-emission tomography (PET) perfusion tracer, 18F BMS747158-02, for the assessment of myocardial infarct (MI) size. Methods and Results—Wistar rats were studied 24 hours after ligation of the left coronary artery either permanently (n=15) or transiently (n=16) for 30 minutes. Seven nonoperated rats were studied as controls. The rats were injected with 37 MBq of 18F BMS747158-02 and imaged with a small animal PET scanner for 20 minutes. Polar maps were generated for measurement of PET defect size, and left ventricular systolic and diastolic volumes were assessed in gated images. As a reference, MI size was determined by 2,3,5-triphenyltetrazolium chloride staining of left ventricular tissue samples. Permanent or transient ligation of the left coronary artery produced transmural or subendocardial MI of variable sizes, respectively. In normal rats, PET imaging demonstrated intense and homogeneous uptake of 18F BMS747158-02 throughout the myocardium. After ligation, sharply defined perfusion defects were present. Throughout the imaging period, the defect size correlated closely with the MI size either after permanent (r=0.88; P<0.01; mean difference, 1.86%) or transient (r=0.92; P<0.01; mean difference, 2.16%) ligation of the left coronary artery. Moreover, reduction of left ventricular systolic function measured with PET correlated with the MI size (r=−0.81; P<0.01; n=23). Conclusions—Myocardial 18F BMS747158-02 PET imaging provides excellent image quality and uptake properties, enabling accurate evaluation of MI size and left ventricular function in rats. It is a promising technique for evaluation of MI size in clinical trials.

Molecular Imaging of Early αvβ3 Integrin Expression Predicts Long-Term Left-Ventricle Remodeling After Myocardial Infarction in Rats

18F-galacto-RGD (18F-RGD) is a PET tracer binding to αvβ3 integrin receptors that are upregulated after myocardial infarction (MI) as part of the healing process. We studied whether myocardial 18F-RGD uptake early after MI is associated with long-term left-ventricle (LV) remodeling in a rat model. Methods: Wistar rats underwent sham operation (n = 9) or permanent coronary ligation (n = 25). One week after MI, rats were injected with 18F-RGD to evaluate αvβ3 integrin expression using a preclinical PET system. In the same rats, LV volumes and defect size were measured 1 and 12 wk after MI by 13N-ammonia PET and MRI, respectively. Results: One week after MI, 18F-RGD uptake was increased in the defect area as compared with the remote myocardium of MI rats or sham-operated controls (percentage injected dose per cubic centimeter, 0.20 ± 0.05 vs. 0.06 ± 0.03 and 0.07 ± 0.04, P < 0.001). At this time, 18F-RGD uptake was associated with capillary density in histologic sections. Average 18F-RGD uptake in the defect area was lowest in the rats demonstrating greater than 20% relative increase in the LV end-diastolic volume from 1 to 12 wk (percentage injected dose per centimeter cubed, 0.15 ± 0.07 vs. 0.21 ± 0.05, P < 0.05). In a multivariable logistic regression analysis, low 18F-RGD uptake was a significant predictor of increase in end-diastolic volume (r = 0.51, P < 0.05). Conclusion: High levels of 18F-RGD uptake in the perfusion defect area early after MI were associated with the absence of significant LV remodeling after 12 wk of follow-up. These results suggest that αvβ3 integrin expression is a potential biomarker of myocardial repair processes after MI and enables the monitoring of these processes by molecular imaging to derive possible prognostic information.

Evaluation of a Novel 18F-Labeled PET Perfusion Tracer for the Assessment of Myocardial Infarct Size in Rat

Background—The goal of this study was to evaluate a new 18F-labeled positron-emission tomography (PET) perfusion tracer, 18F BMS747158-02, for the assessment of myocardial infarct (MI) size. Methods and Results—Wistar rats were studied 24 hours after ligation of the left coronary artery either permanently (n=15) or transiently (n=16) for 30 minutes. Seven nonoperated rats were studied as controls. The rats were injected with 37 MBq of 18F BMS747158-02 and imaged with a small animal PET scanner for 20 minutes. Polar maps were generated for measurement of PET defect size, and left ventricular systolic and diastolic volumes were assessed in gated images. As a reference, MI size was determined by 2,3,5-triphenyltetrazolium chloride staining of left ventricular tissue samples. Permanent or transient ligation of the left coronary artery produced transmural or subendocardial MI of variable sizes, respectively. In normal rats, PET imaging demonstrated intense and homogeneous uptake of 18F BMS747158-02 throughout the myocardium. After ligation, sharply defined perfusion defects were present. Throughout the imaging period, the defect size correlated closely with the MI size either after permanent (r=0.88; P<0.01; mean difference, 1.86%) or transient (r=0.92; P<0.01; mean difference, 2.16%) ligation of the left coronary artery. Moreover, reduction of left ventricular systolic function measured with PET correlated with the MI size (r=−0.81; P<0.01; n=23). Conclusions—Myocardial 18F BMS747158-02 PET imaging provides excellent image quality and uptake properties, enabling accurate evaluation of MI size and left ventricular function in rats. It is a promising technique for evaluation of MI size in clinical trials.

Urinary strem-1 is an early outcome predictor for sepsis and sepsis-induced acute kidney injury.

Methods Thirty critically ill patients (pts.) with sepsis (57.6 ± 7.5 y, 18 males) and a subset of 10 controls (45.6 ± 3.5 y, 7 males) were included in this study. Urinary sTREM-1 and C-reactive protein (CRP) serum levels were measured on admission, day 3 and 7, respectively. SOFA score was estimated at baseline and daily until discharge, death or up to 28 days. ICU length of stay, need for mechanical ventilation, vasopressors or renal replacement therapy, and development of AKI and the final outcome were recorded.

Comparison between H-FABP & troponin i as outcome predictors in sepsis and sepsis-related LV dysfunction

Methods Fifty ICU patients (pts.) with sepsis were enrolled in this study. All pts. were subjected to APACHE II score as a clinical scoring system on admission and every 24 h during the ICU stay. All pts. were also investigated for the serum levels of both H-FABP and Troponin I during the first 24 h after admission. Using modified Simpson ́s method, echocardiographic left ventricular (LV) end-diastolic volume (LVEDV), LV end-systolic volume (LVESV) and LV % ejection fraction (%EF) were calculated on admission and after 24 h.

Fractional excretion of sodium and fractional excretion of urea in differentiating prerenal from renal azotemia complicating circulatory shock.

Methods Both serum FENa & FEurea were measured in 40 patients (pts) with acute kidney injury (AKI) complicating circulatory shock during their stay in ICU. All patients were divided into 26 pts (mean: 60.0 ± 15.15 years) with prerenal azotemia (group-1) and 14 pts (mean: 56.29 ± 19.5 years) with renal azotemia (group-2). Group-1 was subdivided into 12 pts (group-1a) who didn’t receive diuretics 24 hours before the sampling process and 14 pts (group-1b) who received diuretics during their stay in ICU. Acute kidney injury was diagnosed according to the RIFLE-criteria (Risk, Injury, Failure, Loss and End-stage Kidney) in oliguric patients.

Comparison between fractional excretion of sodium and fractional excretion of urea in differentiating prerenal from renal azotemia in circulatory shock

Background: Fractional excretion of sodium (FENa) is used to differentiate renal from prerenal azotemia. However, many drugs and medical conditions affect the sodium (Na+) handling in the kidney. But the fractional excretion of urea (FEurea) is dependent on passive forces and is less influenced by the diuretic therapy. Objective: Comparison between FENa and FEurea in differentiating renal from prerenal azotemia in circulatory shock, and the effect of diuretics on their handling. Methods: Both FENa and FEurea were measured in 40 patients (pts) with AKI complicating circulatory shock. The pts were divided into 26 pts with prerenal (group‐1) and 14 pts with renal azotemia (group‐2). Group‐1 was subdivided into 12 pts who did not receive diuretics 24 h before the sampling process (group‐1a) and 14 pts who received diuretics (group‐1b). Results: Compared to patients with renal azotemia (group‐2), those with prerenal azotemia (group‐1) showed significantly lower FENa (0.99 ± 0.66 and 2.57 ± 1.73, P < 0.05) respectively, and significantly lower FEurea (29.7 ± 7.6 and 43.7 ± 15.4, P < 0.001) respectively. For differentiating renal from prerenal azotemia, compared to FENa, FEurea showed better sensitivity (78.1% vs. 71.4%) and specificity (88.5% vs. 69.4%) respectively. Moreover, FEurea was not significantly affected by the use of diuretics; sensitivity (78% vs. 78%) and specificity (92% vs. 88%) respectively, compared to pts who did not receive diuretics. On the other hand, compared to pts who did not receive diuretics, the use of diuretics significantly affected FENa; sensitivity (64% vs. 71%) and specificity (58% vs. 70%) respectively. Conclusions: FEurea is more sensitive, specific and less affected by the use of diuretics than FENa in differentiating renal from prerenal azotemia in patients with AKI complicating circulatory shock.