Comparison of two software systems for quantification of myocardial blood flow in patients with hypertrophic cardiomyopathy.

BACKGORUND: Quantification of myocardial blood flow (MBF) by positron emission tomography (PET) is important for investigation of angina in hypertrophic cardiomyopathy (HCM). Several software programs exist for MBF quantification, but they have been mostly evaluated in patients (with normal cardiac geometry), referred for evaluation of coronary artery disease (CAD). Software performance has not been evaluated in HCM patients who frequently have hyperdynamic LV function, LV outflow tract (LVOT) obstruction, small LV cavity size, and variation in the degree/location of LV hypertrophy. AIM: We compared results of MBF obtained using PMod, which permits manual segmentation, to those obtained by FDA-approved QPET software which has an automated segmentation algorithm. METHODS: 13N-ammonia PET perfusion data were acquired in list mode at rest and during pharmacologic vasodilation, in 76 HCM patients and 10 non-HCM patients referred for evaluation of CAD (CAD group.) Data were resampled to create static, ECG-gated and 36-frame-dynamic images. Myocardial flow reserve (MFR) and MBF (in ml/min/g) were calculated using QPET and PMod softwares. RESULTS: All HCM patients had asymmetric septal hypertrophy, and 50% had evidence of LVOT obstruction, whereas non-HCM patients (CAD group) had normal wall thickness and ejection fraction. PMod yielded significantly higher values for global and regional stress-MBF and MFR than for QPET in HCM. Reasonably fair correlation was observed for global rest-MBF, stress-MBF, and MFR using these two softwares (rest-MBF: r = 0.78; stress-MBF: r = 0.66.; MFR: r = 0.7) in HCM patients. Agreement between global MBF and MFR values improved when HCM patients with high spillover fractions (> 0.65) were excluded from the analysis (rest-MBF: r = 0.84; stress-MBF: r = 0.72; MFR: r = 0.8.) Regionally, the highest agreement between PMod and QPET was observed in the LAD territory (rest-MBF: r = 0.82, Stress-MBF: r = 0.68) where spillover fraction was the lowest. Unlike HCM patients, the non-HCM patients (CAD group) demonstrated excellent agreement in MBF/MFR values, obtained by the two softwares, when patients with high spillover fractions were excluded (rest-MBF: r = 0.95; stress-MBF: r = 0.92; MFR: r = 0.95). CONCLUSIONS: Anatomic characteristics specific to HCM hearts contribute to lower correlations between MBF/MFR values obtained by PMod and QPET, compared with non-HCM patients. These differences indicate that PMod and QPET cannot be used interchangeably for MBF/MFR analyses in HCM patients.

Correction to: Comparison of two software systems for quantification of myocardial blood flow in patients with hypertrophic cardiomyopathy.

The following information is missing from the Funding footnote on the first page of the published article: "This study was partly funded by NIH RO1 HL092985." The last/corresponding author is incorrectly listed on the first page of the published article: The correct name is Abraham MR.

Stress Myocardial Blood Flow Heterogeneity Is a Positron Emission Tomography Biomarker of Ventricular Arrhythmias in Patients With Hypertrophic Cardiomyopathy.

Patients with hypertrophic cardiomyopathy (HC) are at increased risk of sudden cardiac death. Abnormalities in myocardial blood flow (MBF) detected by positron emission tomography (PET) are common in HC, but a PET marker that identifies patients at risk of sudden cardiac death is lacking. We hypothesized that disparities in regional myocardial perfusion detected by PET would identify patients with HC at risk of ventricular arrhythmias. To test this hypothesis, we quantified global and regional MBFs by 13NH3-PET at rest and at stress, and developed a heterogeneity index to assess MBF heterogeneity in 133 symptomatic patients with HC. The MBF heterogeneity index was computed by dividing the highest by the lowest regional MBF value, at rest and after vasodilator stress, in each patient. High stress MBF heterogeneity was defined as an index of ≧1.85. Patients with HC were stratified by the presence or the absence of ventricular arrhythmias, defined as sustained ventricular tachycardia (VT) and/or nonsustained VT, during follow-up. We found that global and regional MBFs at rest and stress were similar in patients with HC with or without ventricular arrhythmias. Variability in regional stress MBF was observed in both groups, but the stress MBF heterogeneity index was significantly higher in patients with HC who developed ventricular arrhythmias (1.82 ± 0.77 vs 1.49 ± 0.25, p <0.001). A stress MBF heterogeneity index of ≧1.85 was an independent predictor of both sustained VT (hazard ratio 16.1, 95% confidence interval 3.2 to 80.3) and all-VT (sustained-VT + nonsustained VT: hazard ratio 3.7, 95% confidence interval 1.4 to 9.7). High heterogeneity of stress MBF, reflected by an MBF heterogeneity index of ≥1.85, is a PET biomarker for ventricular arrhythmias in symptomatic patients with HC.

A comparison of FLT to FDG PET/CT in the early assessment of chemotherapy response in stages IB-IIIA resectable NSCLC.

BACKGROUND: The aim of this study was to compare the percentage change in 18F-fluorothymidine (FLT) standard uptake value (SUV) between baseline and after one cycle of chemotherapy in patients categorized by RECIST 1.1 computed tomography (CT) as responders or non-responders after two cycles of therapy. Change in 18F-fluorodeoxyglucose (FDG) uptake was also compared between these time points. Nine patients with newly diagnosed, operable, non-small cell lung cancer (NSCLC) were imaged with FDG positron emission tomography/CT (PET), FLT PET/CT, and CT at baseline, following one cycle of neoadjuvant therapy (75 mg/m2 docetaxel + 75 mg/m2 cisplatin), and again after the second cycle of therapy. All patients had a biopsy prior to enrollment and underwent surgical resection within 4 weeks of post-cycle 2 imaging. RESULTS: Between baseline and post-cycle 1, non-responders had mean SULmax (maximum standard uptake value adjusted for lean body mass) increases of 7.0 and 3.4% for FDG and FLT, respectively. Responders had mean decreases of 44.8 and 32.0% in FDG and FLT SULmax, respectively, between baseline and post-cycle 1 imaging. On post-cycle 1 imaging, primary tumor FDG SUL values were significantly lower in responders than in non-responders (P = 0.016). Primary tumor FLT SUL values did not differ significantly between these groups. Using the change from baseline to post-cycle 1, receiver-operating characteristic (ROC) analysis showed an area under the curve (AUC) of 0.94 for FDG and 0.78 for FLT in predicting anatomic tumor response after the second cycle of therapy. CONCLUSIONS: Fractional decrease in FDG SULmax from baseline to post-cycle 1 imaging was significantly different between anatomic responders and non-responders, while percentage changes in FLT SULmax were not significantly different between these groups over the same period of time.

Effect of Diffuse Subendocardial Hypoperfusion on Left Ventricular Cavity Size by 13N-Ammonia Perfusion PET in Patients With Hypertrophic Cardiomyopathy.

Vasodilator-induced transient left ventricular (LV) cavity dilation by positron emission tomography (PET) is common in patients with hypertrophic cardiomyopathy (HC). Because most patients with PET-LV cavity dilation lack obstructive epicardial coronary artery disease, we hypothesized that vasodilator-induced subendocardial hypoperfusion resulting from microvascular dysfunction underlies this result. To test this hypothesis, we quantified myocardial blood flow (MBF) (subepicardial, subendocardial, and global MBF) and left ventricular ejection fraction (LVEF) in 104 patients with HC without significant coronary artery disease, using 13NH3-PET. Patients with HC were divided into 2 groups, based on the presence/absence of LV cavity dilation (LVvolumestress/LVvolumerest >1.13). Transient PET-LV cavity dilation was evident in 52% of patients with HC. LV mass, stress left ventricular outflow tract gradient, mitral E/E', late gadolinium enhancement, and prevalence of ischemic ST-T changes after vasodilator were significantly higher in patients with HC with LV cavity dilation. Baseline LVEF was similar in the 2 groups, but LV cavity dilation+ patients had lower stress-LVEF (43 ± 11 vs 53 ± 10; p <0.001), lower stress-MBF in the subendocardial region (1.6 ± 0.7 vs 2.3 ± 1.0 ml/min/g; p <0.001), and greater regional perfusion abnormalities (summed difference score: 7.0 ± 6.1 vs 3.9 ± 4.3; p = 0.004). The transmural perfusion gradient, an indicator of subendocardial perfusion, was similar at rest in the 2 groups. Notably, LV cavity dilation+ patients had lower stress-transmural perfusion gradients (0.85 ± 0.22, LV cavity dilation+ vs 1.09 ± 0.39, LV cavity dilation-; p <0.001), indicating vasodilator-induced subendocardial hypoperfusion. The stress-transmural perfusion gradient, global myocardial flow reserve, and stress-LVEF were associated with LV cavity dilation. In conclusion, diffuse subendocardial hypoperfusion and myocardial ischemia resulting from microvascular dysfunction contribute to development of transient LV cavity dilation in HC.

Apparent left ventricular cavity dilatation during PET/CT in hypertrophic cardiomyopathy: Clinical predictors and potential mechanisms.

BACKGROUND: Apparent left ventricular cavity dilatation (LVCD) in patients with hypertrophic cardiomyopathy (HCM) is an incompletely understood phenomenon. We aimed at investigating its clinical predictors and potential mechanisms. METHODS: Sixty one HCM patients underwent N-13-ammonia PET for visual evaluation of LVCD, transient ischemic dilatation (TID) index, myocardial blood flow (MBF), coronary flow reserve (CFR), and regional myocardial perfusion (rMP). TID index was also derived at 2-4 and 15-20 minutes. RESULTS: Visual LVCD and quantitative TID (>1.13 abnormal) agreement were excellent (k 0.91; P < .0001). LVCD-positive (n = 32) patients had greater LV thickness (2.26 ± 0.59 vs 1.92 ± 0.41 cm; P = .005), but lower stress MBF (1.66 ± 0.42 vs 2.07 ± 0.46 mL/minute/g; P < .0001), and CFR (1.90 ± 0.46 vs 2.46 ± 0.69; P < .0001) than LVCD-negative (n = 29) patients. Abnormal rMP was present in 31/32 LVCD-positive but only 12/29 (P < .0001) LVCD-negative. TID index was higher at 2-4 (1.30 ± 0.13) than at 15-20 minutes (1.27 ± 0.12; P = .001) in LVCD-positive, whereas it was the same (1.04 ± 0.07 vs 1.04 ± 0.07; P = .9) in LVCD-negative. In multivariate analysis, global peak MBF, abnormal rMP, and LV thickness were the best predictors of LVCD. CONCLUSION: Apparent LVCD is a common finding in HCM, intimately related to abnormal myocardial perfusion, globally impaired vasodilator flow reserve, and degree of hypertrophy. In addition to regional and/or diffuse subendocardial ischemia, some degree of true LV chamber dilatation may also contribute to the occurrence of apparent LVCD in HCM.

Two-time-point FDG PET/CT: liver SULmean repeatability.

OBJECTIVE. The purpose of this study was to evaluate the repeatability of liver mean standardized uptake value normalized to lean body mass (SULmean) in the same patients at different time points within the right lobe of the liver at (18)F-FDG PET/CT, in a clinical setting. MATERIALS AND METHODS. Two PET/CT studies performed on two different dates from each of 130 patients who had normal livers according to structural imaging were included in this reader study. The mean (± SD) length of time between the studies was 235 ± 192 days. SULmean was measured with a 30-mm diameter spherical volume of interest (VOI) placed within the right lobe of the liver (above, below, and at the level of the main portal vein) by two expert readers. ANOVA, intraclass correlation coefficient (ICC), and Bland-Altman analysis were performed. RESULTS. The ICC for the first and second set of studies varied between 0.487 and 0.535 for reader 1 and between 0.472 and 0.545 for reader 2. The mean percentage variation for SULmean between the two time scans for the VOIs placed above, below, and at the level of the main portal vein were 3.55% ± 23.19%, 4.65% ± 23.87%, and 4.30% ± 23.03%, respectively, for reader 1 and 4.49% ± 23.23%, 4.33% ± 23.74%, and 4.48% ± 23.01%, respectively, for reader 2. Using 95% CI, the reference range for intrapatient variations between the studies in liver SULmean was -0.5 to 0.60. CONCLUSION. There is only fair repeatability of liver SULmean measured between two time points in the same patient in a clinical setting. Scan-to-scan intrapatient variation in absolute liver SULmean was -0.5 to 0.60.

Brain FDG PET and the diagnosis of dementia.

OBJECTIVE: We review the role of brain FDG PET in the diagnosis of Alzheimer disease, frontotemporal dementia, dementia with Lewy bodies, and vascular dementia. Characteristic spatial patterns of brain metabolism on FDG PET can help differentiate various subtypes of dementia. CONCLUSION: In patients with different subtypes of dementia, FDG PET/CT shows distinct spatial patterns of metabolism in the brain and can help clinicians to make a reasonably accurate and early diagnosis for appropriate management or prognosis.

Liver standardized uptake value corrected for lean body mass at FDG PET/CT: effect of FDG uptake time.

OBJECTIVE: The objective of this study is to establish the magnitude change and interreader reliability of the liver standardized uptake value corrected for lean body mass (SULmean) in dual-time-point imaging at 1 and 2 hours and 1 and 4 hours. PATIENTS AND METHODS: Early and delayed FDG PET/CT scans were included for 28 patients (13 men and 15 women) who had normal liver by CT or ultrasound. The average uptake time between the early and delayed scans were 55 minutes (range, 44-69 minutes) for pancreatic adenocarcinoma patients (n = 19) and 184 minutes (range, 140-197 minutes) for neurofibromatosis patients (n = 9). A 30-mm-diameter spherical volume of interest was placed within the right lobe of the liver above, below, and at the level of the main portal vein by 2 independent readers. Correlation coefficients, analysis of variance, intraclass correlation coefficient, and Bland-Altman analysis were performed. RESULTS: The mean liver SULmean was between 1.39 and 1.42 and between 1.28 and 1.3 in early and delayed images, respectively (P = 0.001). There is time-dependent reduction in the mean liver SULmean at 2-hour (7%-8%) and 4-hour uptake time (15%-21%) compared with 1-hour uptake time. The correlation coefficient between delayed uptake time and liver SULmean reduction is 0.39 to 0.41 at the upper aspect of the liver. The intraclass correlation coefficient for 2 readers varied between 0.997 and 0.998 and between 0.995 and 0.999 in early and delayed images, respectively (P = 0.001). CONCLUSIONS: There is time-dependent reduction of mean liver SULmean, about 7% to 8% within the clinically relevant FDG uptake time, in the same patient with excellent interreader agreement in early and delayed images within the right lobe of the liver. Therefore, liver SULmean could represent a useful reference parameter in quantitative analysis of dual-phase FDG PET/CT in malignancy or atypical infection/inflammatory disease. Furthermore, it may be suitable as a normalization factor in currently available formulae quantifying therapy response on PET imaging.

Prognostic value of FDG PET metabolic tumor volume in human papillomavirus-positive stage III and IV oropharyngeal squamous cell carcinoma.

OBJECTIVE: The purpose of this study was to establish the prognostic utility in human papillomavirus (HPV)-positive stage III and IV oropharyngeal squamous cell carcinoma (SCC) of the (18)F-FDG parameters maximal, mean, and peak standardized uptake value (SUVmax, SUVmean, and SUVpeak, respectively); metabolic tumor volume (MTV); and total lesion glycolysis (TLG). MATERIALS AND METHODS: We included 70 patients in the present study who had a biopsy-proven HPV-positive (by in situ hybridization) stage III and IV oropharyngeal SCC and had a baseline PET/CT examination at our institution. Outcome endpoint was event-free survival (EFS), which included recurrence-free and overall survival. Cox proportional hazards multivariate regression analyses were performed. Survival analysis was performed using Kaplan-Meier survival curves. RESULTS: In Cox regression proportional hazard univariate analysis, total MTV (hazard ratio [HR], 1.02; p = 0.008), primary-tumor MTV (HR, 1.02; p = 0.024), neck nodal MTV (HR, 1.03; p = 0.006), neck nodal TLG (HR, 1.01; p = 0.006), and neck node status (HR, 4.45; p = 0.03) showed a statistically significant association with EFS. There was no statistically significant association of EFS with SUVmax, SUVmean, SUVpeak, and primary-tumor or overall TLG. In Cox regression proportional hazard multivariate model I, total MTV remained an independent prognostic marker for EFS when adjusted for every other variable individually in the model; in model II, primary-tumor MTV, neck node status, and SUVpeak are independent prognostic markers for EFS. The Kaplan-Meier survival curves using optimum cut point of 41 mL of total MTV were not significant (p = 0.09). CONCLUSION: Total MTV and primary-tumor MTV are associated with survival outcomes in patients with HPV-positive stage III and IV oropharyngeal SCC.

Optimum lean body formulation for correction of standardized uptake value in PET imaging.

UNLABELLED: Standardized uptake value (SUV) normalized by lean body mass ([LBM] SUL) is becoming a popular metric for quantitative assessment of clinical PET. Sex-specific quantitative effects of different LBM formulations on liver SUV have not been well studied. METHODS: (18)F-FDG PET/CT scans from 1,033 consecutive adult (501 women, 532 men) studies were reviewed. Liver SUV was measured with a 3-cm-diameter spheric region of interest in the right hepatic lobe and corrected for LBM using the sex-specific James and Janmahasatian formulations. RESULTS: Body weight was 71.0 ± 20.7 kg (range, 18.0-175.0 kg) and 82.9 ± 18.6 kg (range, 23.0-159.0 kg) for women and men, respectively. SUV, based on body weight, has a significantly positive correlation with weight for both women (r = 0.58, P < 0.0001) and men (r = 0.54, P < 0.0001). This correlation is reduced in men (r = 0.11, P = 0.01) and becomes negative for women (r = -0.35, P = 0.0001) with the James formulation of SUL. This negative correlation was eliminated when the very obese women (body mass index ≥ 35) were excluded from the analysis (r = 0.13, P = 0.8). The Janmahasatian formulation annuls the correlation between SUL and weight for women (r = 0.04, P = 0.4) and decreases it for men (r = 0.13, P = 0.003). CONCLUSION: Hepatic correction with the more common James formulation for body lean mass breaks down and shows low SUL values in very obese patients. The adoption of the Janmahasatian formula for estimation of LBM in modern PET scanners and display workstations is recommended, in view of the increasing frequency of obesity.

Head and neck PET/CT: therapy response interpretation criteria (Hopkins Criteria)-interreader reliability, accuracy, and survival outcomes.

UNLABELLED: There has been no established qualitative system of interpretation for therapy response assessment using PET/CT for head and neck cancers. The objective of this study was to validate the Hopkins interpretation system to assess therapy response and survival outcome in head and neck squamous cell cancer patients (HNSCC). METHODS: The study included 214 biopsy-proven HNSCC patients who underwent a posttherapy PET/CT study, between 5 and 24 wk after completion of treatment. The median follow-up was 27 mo. PET/CT studies were interpreted by 3 nuclear medicine physicians, independently. The studies were scored using a qualitative 5-point scale, for the primary tumor, for the right and left neck, and for overall assessment. Scores 1, 2, and 3 were considered negative for tumors, and scores 4 and 5 were considered positive for tumors. The Cohen κ coefficient (κ) was calculated to measure interreader agreement. Overall survival (OS) and progression-free survival (PFS) were analyzed by Kaplan-Meier plots with a Mantel-Cox log-rank test and Gehan Breslow Wilcoxon test for comparisons. RESULTS: Of the 214 patients, 175 were men and 39 were women. There was 85.98%, 95.33%, 93.46%, and 87.38% agreement between the readers for overall, left neck, right neck, and primary tumor site response scores, respectively. The corresponding κ coefficients for interreader agreement between readers were, 0.69-0.79, 0.68-0.83, 0.69-0.87, and 0.79-0.86 for overall, left neck, right neck, and primary tumor site response, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy of the therapy assessment were 68.1%, 92.2%, 71.1%, 91.1%, and 86.9%, respectively. Cox multivariate regression analysis showed human papillomavirus (HPV) status and PET/CT interpretation were the only factors associated with PFS and OS. Among the HPV-positive patients (n = 123), there was a significant difference in PFS (hazard ratio [HR], 0.14; 95% confidence interval, 0.03-0.57; P = 0.0063) and OS (HR, 0.01; 95% confidence interval, 0.00-0.13; P = 0.0006) between the patients who had a score negative for residual tumor versus positive for residual tumor. A similar significant difference was observed in PFS and OS for all patients. There was also a significant difference in the PFS of patients with PET-avid residual disease in one site versus multiple sites in the neck (HR, 0.23; log-rank P = 0.004). CONCLUSION: The Hopkins 5-point qualitative therapy response interpretation criteria for head and neck PET/CT has substantial interreader agreement and excellent negative predictive value and predicts OS and PFS in patients with HPV-positive HNSCC.

Follow-up or Surveillance (18)F-FDG PET/CT and Survival Outcome in Lung Cancer Patients.

UNLABELLED: The value of performing follow-up PET/CT imaging more than 6 mo after the conclusion of therapy-either as a routine practice or because of clinically suspected recurrence-is not well established. The purpose of this study was to evaluate the added value of follow-up PET/CT to the clinical assessment and survival outcome of lung cancer patients. METHODS: This was a retrospective study of 261 biopsy-proven lung cancer patients at a single tertiary center. In total, 488 follow-up PET/CT scans done 6 or more months after the completion of initial treatment were included in this study. Median follow-up from the completion of primary treatment was 29.3 mo (range, 6.1-295.1 mo). Overall survival (OS) benefit was measured using Kaplan-Meier plots with a Mantel-Cox log-rank test. A multivariate Cox regression model was provided with clinical covariates. RESULTS: Of the 488 PET/CT scans, 281 were positive and 207 negative for recurrence. Overall median survival from the time of the PET/CT study was 48.5 mo. The median survival of PET-positive and PET-negative groups was 32.9 and 81.6 mo, respectively (P < 0.0001). A subgroup analysis demonstrated a similar difference in OS for 212 scans completed between 6 and 24 mo after treatment (P = 0.0004) and 276 scans completed after 24 mo (P = 0.0006). In the context of clinical assessment, PET/CT identified recurrence in 43.7% (107/245) of scans without prior clinical suspicion and ruled out recurrence in 15.2% (37/243) of scans with prior clinical suspicion. There was a significant difference in OS when grouped by clinical suspicion (P = 0.0112) or routine follow-up (P < 0.0001). In a multivariate Cox regression model, factors associated with OS were age (P < 0.0001) and PET/CT result (P = 0.0003). An age-stratified subgroup analysis demonstrated a significant difference in OS by PET scan result among patients younger than 60 y and between 60 and 70 y but not in those older than 70 y (P < 0.0001, P = 0.0004, and P = 0.8193, respectively). CONCLUSION: (18)F-FDG PET/CT performed for follow-up more than 6 mo after the completion of primary treatment adds value to clinical judgment and is a prognostic marker of OS in lung cancer patients, regardless of the timing of the follow-up scan, and especially in patients younger than 70 y.

SPECT analysis of cardiac perfusion changes after whole-breast/chest wall radiation therapy with or without active breathing coordinator: results of a randomized phase 3 trial.

PURPOSE: Cardiac muscle perfusion, as determined by single-photon emission computed tomography (SPECT), decreases after breast and/or chest wall (BCW) irradiation. The active breathing coordinator (ABC) enables radiation delivery when the BCW is farther from the heart, thereby decreasing cardiac exposure. We hypothesized that ABC would prevent radiation-induced cardiac toxicity and conducted a randomized controlled trial evaluating myocardial perfusion changes after radiation for left-sided breast cancer with or without ABC. METHODS AND MATERIALS: Stages I to III left breast cancer patients requiring adjuvant radiation therapy (XRT) were randomized to ABC or No-ABC. Myocardial perfusion was evaluated by SPECT scans (before and 6 months after BCW radiation) using 2 methods: (1) fully automated quantitative polar mapping; and (2) semiquantitative visual assessment. The left ventricle was divided into 20 segments for the polar map and 17 segments for the visual method. Segments were grouped by anatomical rings (apical, mid, basal) or by coronary artery distribution. For the visual method, 2 nuclear medicine physicians, blinded to treatment groups, scored each segment's perfusion. Scores were analyzed with nonparametric tests and linear regression. RESULTS: Between 2006 and 2010, 57 patients were enrolled and 43 were available for analysis. The cohorts were well matched. The apical and left anterior descending coronary artery segments had significant decreases in perfusion on SPECT scans in both ABC and No-ABC cohorts. In unadjusted and adjusted analyses, controlling for pretreatment perfusion score, age, and chemotherapy, ABC was not significantly associated with prevention of perfusion deficits. CONCLUSIONS: In this randomized controlled trial, ABC does not appear to prevent radiation-induced cardiac perfusion deficits.

Initial human experience with Rubidium-82 renal PET/CT imaging.

INTRODUCTION: Preclinical data have shown that Rubidium-82 chloride ((82)Rb) is a radiotracer with high first pass extraction and slow washout in the kidneys. The goal of this study was to investigate the feasibility of human kidney imaging with (82)Rb positron emission tomography (PET) and obtain quantitative data of its uptake non-invasively. METHODS: Eight healthy volunteers underwent dynamic PET/CT imaging with (82)Rb. A preprogrammed pump was used to insure reproducible injections. Tissue time activity curves were generated from the renal cortex. An input function was derived from the left ventricular blood pool (LVBP), the descending thoracic aorta and the abdominal aorta. Renal blood flow was estimated by applying a two-compartment kinetic model. Results obtained with different input functions were compared. RESULTS: Radiotracer accumulation was rapid and reached a plateau within 15-30 s after the bolus entered the kidneys. The derived K1 and k2 parameters were reproducible using input functions obtained from diverse vascular locations. K1 averaged 1.98 ± 0.14 mL/min/g. The average k2 was 0.35 ± 0.11/min. Correlation between K1 values obtained from the LVBP from different bed positions when the kidneys and abdominal aorta were in the same field of view was excellent (R = 0.95). CONCLUSIONS: Non-invasive quantitative human kidney imaging with (82)Rb PET is feasible. Advantages of renal PET with (82)Rb include excellent image quality with high image resolution and contrast. (82)Rb has potential as a clinical renal imaging agent in humans.

PET/CT imaging and human papilloma virus-positive oropharyngeal squamous cell cancer: evolving clinical imaging paradigm.

Human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) represents an emerging disease that differs from HPV-negative OPSCC in natural history and prognosis. Contrast-enhanced PET/CT is essential to accurately stage the primary site when there are smaller tumors; neck nodal metastases, which tend to have a more cystic component; and distant metastases that manifest in unusual sites (disseminating phenotype) such as bones and other solid organs, including brain. Metastases tend to appear later in the disease course during follow-up for HPV-positive OPSCC than for HPV-negative OPSCC. Because HPV-positive OPSCC patients have a better clinical outcome, there is a need for treatment deintensification to spare the patient from treatment-related toxicities. (18)F-FDG PET/CT would play a role in monitoring patients with deintensified treatments to ensure that no adverse outcome is introduced. The better prognosis and outcome of HPV-positive OPSCC patients would warrant imaging follow-up that is less intense but continues longer because of the manifestation of distant metastases later in the disease course and at unusual sites. All these clinical paradigms facilitate a definite role for PET/CT imaging in the management of HPV-positive OPSCC.

Respiratory-gated PET/CT versus delayed images for the quantitative evaluation of lower pulmonary and hepatic lesions.

PURPOSE: Respiratory motion degrades fluorodeoxyglucose positron emission tomography (FDG PET) images of the lower chest and upper abdomen, as the blur introduced by breathing motion increases the apparent size of the moving tumour lesions and decreases their apparent uptake, reducing the sensitivity of PET in detection of small lesions. We assessed the role of delayed and respiratory-gated PET acquisition in the quantitative evaluation of lung and liver lesions. METHODS: A retrospective analysis of 64 lesions was performed. After initial non-gated whole-body PET/CT, respiratory gating was performed with 15 min in list mode. Non-gated delayed images were obtained by summing all list mode data. SUV(max) adjusted for lean body mass (SUL(max)) was measured in the initial whole-body scan, the delayed non-gated scans and the individual gated bins for each lesion. The axial z-position of SUL(max) for each lesion in five respiratory-gated bins was determined. The mean SUL of the non-pathological liver parenchyma was also recorded for each patient. RESULTS: Tumour lesion SUL(max) increased by an average of 34% in the delayed non-gated scan as compared with the whole-body initial scan and further by an additional 17.2% in respiratory-gated images. The maximum lesion displacement was 6.2 ± 5.0 mm. CONCLUSION: Delayed imaging alone substantially increases the magnitude of the SUL of liver and lung lesions as compared with standard whole-body images and may allow for a more accurate definition of the lesion's volume and localisation and improve tracer quantitation in malignant lesions in the lungs or upper abdomen. While respiratory gating provides more optimal imaging with greatest increase in SUL(max), the benefit is small, and delayed imaging appears sufficient in most cases.

Quantitative FDG PET/CT in the community: experience from interpretation of outside oncologic PET/CT exams in referred cancer patients.

PURPOSE: Tertiary care institutions often deal with patients who have had a baseline positron emission tomography (PET)/computed tomography (CT) scan performed elsewhere. Little data exist regarding the quality of these PET/CT scans and whether they are fully suitable for qualitative or quantitative interpretation. We evaluated outside PET/CT scans from cancer patients referred to our institution and compared them with PET/CT scans acquired locally. METHODS: This Health Insurance Portability and Accountability Act-compliant retrospective study was approved by our institutional review board. Informed consent requirements were waived. One hundred seventy recent whole-body outside PET/CT exams from many sites were digitally imported into our radiology imaging system and reviewed for key quality metrics including time from injection until imaging, availability of patient height and weight information, serum glucose level and [(18) F]fluoro-2-deoxy-D-glucose (FDG) dose. The standardised uptake value (SUV) and SUV based on lean body mass (SUL) in the liver were measured whenever possible. These were compared with 170 internal studies performed at our centre during the same period. RESULTS: Missing data were common in outside scans with height in 62%, weight 35%, uptake time 25%, FDG dose 28% and glucose levels in 64% of cases. In quantitatively evaluable cases, mean liver SUL, SUV, FDG dose and uptake time were much more variable in outside than in internal studies. CONCLUSION: Approximately one-third of the outside PET/CT studies submitted digitally for analysis lacked key information required to secure any quantitative imaging data. Only about a third of these studies had all necessary information available for accurate SUL determination and had acceptable quality that was comparable with locally acquired scans. This suggests that many of PET studies performed in the community cannot be relied upon to provide quantitative image data that can be applied in a different centre. Greater standardisation of oncologic PET/CT studies among different centres must still be pursued.

Absolute myocardial flow quantification with (82)Rb PET/CT: comparison of different software packages and methods.

PURPOSE: In clinical cardiac (82)Rb PET, globally impaired coronary flow reserve (CFR) is a relevant marker for predicting short-term cardiovascular events. However, there are limited data on the impact of different software and methods for estimation of myocardial blood flow (MBF) and CFR. Our objective was to compare quantitative results obtained from previously validated software tools. METHODS: We retrospectively analyzed cardiac (82)Rb PET/CT data from 25 subjects (group 1, 62 ± 11 years) with low-to-intermediate probability of coronary artery disease (CAD) and 26 patients (group 2, 57 ± 10 years; P=0.07) with known CAD. Resting and vasodilator-stress MBF and CFR were derived using three software applications: (1) Corridor4DM (4DM) based on factor analysis (FA) and kinetic modeling, (2) 4DM based on region-of-interest (ROI) and kinetic modeling, (3) MunichHeart (MH), which uses a simplified ROI-based retention model approach, and (4) FlowQuant (FQ) based on ROI and compartmental modeling with constant distribution volume. RESULTS: Resting and stress MBF values (in milliliters per minute per gram) derived using the different methods were significantly different: using 4DM-FA, 4DM-ROI, FQ, and MH resting MBF values were 1.47 ± 0.59, 1.16 ± 0.51, 0.91 ± 0.39, and 0.90 ± 0.44, respectively (P<0.001), and stress MBF values were 3.05 ± 1.66, 2.26 ± 1.01, 1.90 ± 0.82, and 1.83 ± 0.81, respectively (P<0.001). However, there were no statistically significant differences among the CFR values (2.15 ± 1.08, 2.05 ± 0.83, 2.23 ± 0.89, and 2.21 ± 0.90, respectively; P=0.17). Regional MBF and CFR according to vascular territories showed similar results. Linear correlation coefficient for global CFR varied between 0.71 (MH vs. 4DM-ROI) and 0.90 (FQ vs. 4DM-ROI). Using a cut-off value of 2.0 for abnormal CFR, the agreement among the software programs ranged between 76 % (MH vs. FQ) and 90 % (FQ vs. 4DM-ROI). Interobserver agreement was in general excellent with all software packages. CONCLUSION: Quantitative assessment of resting and stress MBF with (82)Rb PET is dependent on the software and methods used, whereas CFR appears to be more comparable. Follow-up and treatment assessment should be done with the same software and method.