Alin Chirindel

Evolving role of FDG PET/CT in multiple myeloma imaging and management.

OBJECTIVE Multiple myeloma is the most common cause of primary malignancy in bones. Radiography has been the imaging reference standard for decades. However, the growing use of CT, MRI, and PET technology has led to earlier diagnosis of multiple myeloma, more accurate therapy assessment, and better prediction of patient outcome. This article is focused on the evolving role of (18)F-FDG PET/CT in multiple myeloma diagnosis, therapy assessment, and prognosis. CONCLUSION FDG PET/CT is a valuable imaging modality in diagnosis, therapy assessment, and prognosis of multiple myeloma.

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.

FDG Volumetric Parameters and Survival Outcomes After Definitive Chemoradiotherapy in Patients With Recurrent Head and Neck Squamous Cell Carcinoma

OBJECTIVE The purpose of this study was to establish the predictive value of (18)F-FDG parameters for overall survival in biopsy-proven recurrent head and neck squamous cell cancer (HNSCC) patients after definitive chemoradiotherapy. MATERIALS AND METHODS We conducted a retrospective study including 34 patients with HNSCC who had biopsy-proven recurrence between April 2004 and March 2012 and underwent FDG PET/CT at our institution at the time of recurrence. Maximum standardized uptake value (SUVmax), peak SUV (SUVpeak), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured. The primary outcome measure was overall survival. ROC analysis, univariate and multivariate Cox regression models, and Kaplan-Meir survival curves were performed. RESULTS In univariate analyses, human papillomavirus (HPV) status (p = 0.04), primary site recurrence of MTV (p = 0.03), metastasis of MTV (p = 0.02), metastasis of TLG (p = 0.02), total MTV (p = 0.002), and total TLG (p = 0.04) were significantly associated with overall survival outcome. Total MTV remained as significant independent prognostic factor when adjusted for all other covariates except for primary site recurrence SUVmax and SUVpeak and lymph node SUVmax and SUVpeak. There was a significant difference in time to survival between patients with total MTV above and below the 50th percentile (Mantel-Cox log-rank test, p = 0.05 and Gehan-Breslow-Wilcoxon test, p = 0.03) and the optimum threshold of 16.8 mL (Mantel-Cox log-rank test, p = 0.01 and Gehan-Breslow-Wilcoxon test, p = 0.01; hazard ratio [HR], 0.25). CONCLUSION FDG PET/CT-based total MTV and clinical HPV status may be significant prognostic markers for overall survival of patients with recurrent HNSCC after definitive chemoradiotherapy.

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.

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.

Assessment of Response to Therapy

In modern clinical oncology, there is a growing need to identify response to treatment to detect improvement or worsening of the disease as early as possible. Anatomical imaging modalities that rely on morphologic or structural data, though precise in the delineation of lesions, do not provide functional information about response and have limited reproducibility. The accuracy of anatomical parameters is limited partly due to the delay between the treatment and the appearance of tumor shrinkage. As the changes in tumor metabolism precede the changes in tumor size, functional imaging modalities are more clinically useful and allow visualization of tumor response at earlier stages. PET provides information regarding the metabolic behavior of the disease, independent of morphological and anatomical criteria. This chapter reviews the current evidence on the potential contribution of PET to evaluation of response to therapy and the challenges ahead, especially the standardization of performing clinical PET/CT across centers, to be meaningful in patient care.

Quantitative PET/CT in clinical practice: Assessing the agreement of PET tumor indices using different clinical reading platforms

Objective The aim of this study was to determine whether various fluorine-18-fluorodeoxyglucose PET/CT-derived parameters used in oncology vary significantly depending on the interpretation software systems used in clinical practice for multiple human solid tumors. Patients and methods A total of 120 fluorine-18-fluorodeoxyglucose PET/CT studies carried out in patients with pancreatic, lung, colorectal, and head and neck cancers were evaluated retrospectively on two different vendor software platforms including Mirada and MIMVista. Regions of interest were placed on the liver to determine the liver mean standardized uptake value at lean body mass (SUL) and on each tumor to determine the SULmax, SULpeak. Total lesion glycolysis (TLG) and metabolic tumor volume (MTV) were determined using fixed thresholds of 50% of SULmax and SULpeak. Inter-reader, intersystem intraclass correlations, systematic bias, and variability reflected by the 95% limits of agreement, and precision were determined. Results There was excellent inter-reader reliability between the readers and the two software systems, with intraclass correlations more than 0.9 for all PET metrics, with P values less than 0.0001. The bias and SD on Bland–Altman analysis between the two software platforms for tumor SULmax, SULpeak, Max50MTV, and Peak50MTV, respectively, for Reader 1 were −1.52±2.24, 0.80±3.67, −0.80±13.01, and −4.49±20.6. For Reader 2, the biases were −1.62±1.95, 0.18±3.60, −0.27±4.64, and −3.13±8.30. The precision between the two systems was better for SULmax and SULpeak, with less variance observed, than for volume-based metrics such as Max50MTV and Peak50MTV or TLG. Conclusion Excellent correlation has been found between two tested software reading platforms for all PET-derived metrics in a dual-reader analysis. Overall, the SULmax and SULpeak values had less bias and better precision compared with the MTV and TLG.

ROC-analysis of quantitative early and delayed PET SUL in malignant peripheral nerve sheath tumors (MPNST) versus neurofibroma (BT)

Molecular imaging techniques have advanced and become invaluable tools for molecular biology research and, to a more modest extent, clinical medicine. Molecular imaging is not limited to specific imaging methods but includes optical, scintigraphic, MRI, and MR spectroscopic systems. All these techniques use tagged probes with high affinity for molecules of interest, binding-activatable probes, and genetically engineered stable reporters for optimized target visualization. Therefore, the list of investigated biologic processes is long and continues to expand. This handbook describes a rich variety of practical procedures and methods for diverging imaging technologies. Thirty-eight expert researchers explore the latest advances in molecular imaging, describing a rich variety of practical procedures and methods for diverging imaging methods. This book is organized into 3 sections, and the first section, dealing with imaging biochemical pathways and molecular events, has 5 chapters about bioluminescence resonance energy transfer imaging, luciferase protein complementation assays, hybrid Raman-fluorescence microscopy, labeling of mesenchymal stem cells, and quantification of micro-RNA abundance. Section II, on imaging in preclinical settings, has 7 chapters discussing the imaging fate of stem cells, MRI of brain inflammation, optical characterization of arterial apoptosis, intravital fluorescence microscopic molecular imaging of atherosclerosis, MRI of transplanted stem cells, imaging of epidermal growth factor receptor variants in glioblastomas, and fluorescence-based molecular imaging. Section III, handling clinical imaging, has 4 chapters dealing with PET of angiogenesis using integrin, amyloid imaging, myocardial molecular imaging, and dual-radionuclide brain SPECT for parkinsonian diagnosis. Composed in the highly successful “Methods in Molecular Biology” series format, each chapter contains a brief introduction, step-by-step methods, a list of necessary materials, and tips on troubleshooting and avoiding known pitfalls. Images are clear and informative. This sufficiently detailed handbook is essential for students, research fellows, and established practitioners from different fields to become familiar with molecular imaging and incorporate it into their work. I highly recommend the book to trainees and practitioners in nuclear medicine and radiology with research interest in molecular imaging.