Krishna Alluri

Scoring of coronary artery calcium scans: History, assumptions, current limitations, and future directions

Coronary artery calcium (CAC) scanning is a reliable, noninvasive technique for estimating overall coronary plaque burden and for identifying risk for future cardiac events. Arthur Agatston and Warren Janowitz published the first technique for scoring CAC scans in 1990. Given the lack of available data correlating CAC with burden of coronary atherosclerosis at that time, their scoring algorithm was remarkable, but somewhat arbitrary. Since then, a few other scoring techniques have been proposed for the measurement of CAC including the Volume score and Mass score. Yet despite new data, little in this field has changed in the last 15 years. The main focus of our paper is to review the implications of the current approach to scoring CAC scans in terms of correlation with the central disease - coronary atherosclerosis. We first discuss the methodology of each available scoring system, describing how each of these scores make important indirect assumptions in the way they account (or do not account) for calcium density, location of calcium, spatial distribution of calcium, and microcalcification/emerging calcium that might limit their predictive power. These assumptions require further study in well-designed, large event-driven studies. In general, all of these scores are adequate and are highly correlated with each other. Despite its age, the Agatston score remains the most extensively studied and widely accepted technique in both the clinical and research settings. After discussing CAC scoring in the era of contrast enhanced coronary CT angiography, we discuss suggested potential modifications to current CAC scanning protocols with respect to tube voltage, tube current, and slice thickness which may further improve the value of CAC scoring. We close with a focused discussion of the most important future directions in the field of CAC scoring.

FDG PET/CT imaging of oropharyngeal squamous cell carcinoma: Characteristics of human papillomavirus-positive and -negative tumors

Objective The objective of this study was to assess differences in morphological and glycolytic characteristics of primary tumors and locoregional nodal disease between human papillomavirus (HPV)–positive and HPV-negative oropharyngeal head and neck squamous cell carcinoma. Methods This was a retrospective analysis of 123 baseline FDG PET/CT scans from patients (aged 57.0 ± 10.6 years) with newly diagnosed oropharyngeal SCC between January 2003 and June 2012. There were 98 HPV-positive and 25 HPV-negative patients. SUVmax, SUVpeak, and SUVmean based on lean body mass, as well as RECIST (Response Evaluation Criteria In Solid Tumors) dimensions, metabolic tumor volume (gradient and threshold-segmentation methods) and total lesion glycolysis, were determined for primary and locoregional nodal disease. Results Human papillomavirus–negative primary tumors were significantly larger as measured by RECIST longest diameter (P = 0.002) and slightly more heterogeneous as measured by the heterogeneity index (P = 0.07), higher SUVmax (P < 0.01), SUVpeak (P = 0.01), SUVmean (P = 0.01), metabolic tumor volume (P = 0.002), and total lesion glycolysis (P = 0.001), for both segmentation methods. Index parameters of HPV-positive nodal disease tend to be larger, but some with no statistical significance (P > 0.05). There was no significant difference in the metabolic parameters of primary tumor or nodal metastases for HPV-positive patients with and without smoking history. Conclusions Index morphologic and glycolytic parameters as measured in FDG PET/CT are significantly larger in HPV-negative as compared with HPV-positive primary oropharyngeal carcinoma. In contrast, the same parameters trended to be larger in HPV-positive regional nodal disease.

Addition of 18F-FDG PET/CT to Clinical Assessment Predicts Overall Survival in HNSCC: A Retrospective Analysis with Follow-up for 12 Years

18F-FDG PET/CT is used in the follow-up of patients with head and neck squamous cell cancer (HNSCC). However, its impact on clinical decision making and patient outcome is not fully established. The objective of this study was to determine the prognostic value of 18F-FDG PET/CT for overall survival (OS) of HNSCC patients when performed in addition to clinical assessment between 4 and 24 mo after treatment. Methods: This was a retrospective study at a single tertiary center. The institutional review board approved this study, and the requirement to obtain informed consent was waived. The study included 134 biopsy-proven HNSCC patients with 227 follow-up PET/CT scans. The primary outcome measure was OS. Median follow-up was 40 mo (range, 7–145 mo). Survival is presented as Kaplan–Meier plots with Mantel–Cox log-rank test. The multivariate Cox model included clinical covariates. Results: Of the 227 PET/CT scans, 41 (18%) were positive for tumor and 186 (82%) were negative for tumor. PET/CT identified recurrence in 5% (9/194) of scans performed without prior clinical concern and ruled out tumor in 51.5% (17/33) of scans performed to evaluate clinical suspicion or uncertainty of recurrence. The median survival of PET-positive and -negative groups from the date of the scan was 20 and 30.5 mo, respectively (P < 0.0001). There was a significant difference in OS from the scan date between patients who had a positive PET/CT result for tumor and those who had a negative result (log-rank, P < 0.0001), with a hazard ratio of 29.74. Human papillomavirus status (P = 0.001) and PET/CT result (P = 0.04) were the only factors significantly associated with OS, adjusted for all other covariates. Conclusion: 18F-FDG PET/CT performed between 4 and 24 mo after treatment adds value to clinical assessment at the time of the study, especially when there is clinical suspicion or uncertainty, and can serve as a prognostic marker of OS in HNSCC.

Prognostic Value of FDG PET/CT-Derived Parameters in Pancreatic Adenocarcinoma at Initial PET/CT Staging.

OBJECTIVE The purpose of this study is to evaluate the performance of PET-derived parameters as prognostic markers for overall survival (OS) and progression-free survival (PFS) outcome in patients with pancreatic adenocarcinoma. MATERIALS AND METHODS We conducted a retrospective study of 106 patients (62 men and 44 women) with histologically proven pancreatic adenocarcinoma who underwent initial staging FDG PET/CT before treatment. Peak standardized uptake value (SUV), maximum SUV (SUVmax), metabolic tumor volume, and tumor glycolytic activity of the primary pancreatic tumor were measured. Two segmentation methods were performed to obtain the metabolic tumor volume and tumor glycolytic activity for all tumors: a gradient-based segmentation model (metabolic tumor volume and tumor glycolytic activity by gradient edge detection) and a fixed-threshold model with a threshold of 50% of the lesions SUVmax and peak SUV. Univariate and multivariate Cox regression models were developed including clinical and imaging parameters for OS and PFS. RESULTS Multivariate Cox regression analysis showed a statistically significant association between PFS and age, SUVmax, peak SUV, and tumor glycolytic activity by gradient edge detection. There was a statistically significant difference in PFS for patients with values above and below the median cutoff points for SUVmax (hazard ratio [HR], 1.12; p < 0.01), peak SUV (HR, 1.25; p < 0.02), and tumor glycolytic activity measured by gradient edge detection (HR, 1.00; p < 0.02) of the primary tumor. However, multivariate Cox regression analysis showed a statistically significant association only between tumor glycolytic activity by gradient edge detection and OS (p = 0.04), and there was a statistically significant difference in OS between patients with values above and below the median cutoff point for the tumor glycolytic activity by gradient edge detection of the primary tumor (HR, 1.42; p = 0.05). CONCLUSION Age, SUVmax, peak SUV, and total lesion glycolysis (i.e., tumor glycolytic activity) of the primary tumor are associated with PFS, and tumor glycolytic activity is associated with OS in patients with pancreatic adenocarcinoma.

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.

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. 18F-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.

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.