Faculty Bibliography

Although visual assessment using the Deauville criteria is strongly recommended by guidelines for treatment response monitoring in all FDG-avid lymphoma histologies, the high rate of false-positives and concerns about interobserver variability have motivated the development of quantitative tools to facilitate objective measurement of tumor response in both routine and clinical trial settings. Imaging studies using functional quantitative measures play a significant role in profiling oncologic processes. These quantitative metrics allow for objective end points in multicenter clinical trials. However, the standardization of imaging procedures including image acquisition parameters, reconstruction and analytic measures, and validation of these methods are essential to enable an individualized treatment approach. A robust quality control program associated with the inclusion of proper scanner calibration, cross-calibration with dose calibrators and across other scanners is required for accurate quantitative measurements. In this section, we will review the technical and methodological considerations related to PET-derived quantitative metrics and the relevant published data to emphasize the potential value of these metrics in the prediction of patient prognosis in lymphoma.

A multi-center imaging trial by the American College of Radiology Imaging Network (ACRIN) "A Multicenter, phase II assessment of tumor hypoxia in glioblastoma using 18F Fluoromisonidazole (FMISO) with PET and MRI (ACRIN 6684)", was conducted to assess hypoxia in patients with glioblastoma (GBM). The aims of this study were to support the role of proton magnetic resonance spectroscopic imaging (1H MRSI) as a prognostic marker for brain tumor patients in multi-center clinical trials. Seventeen participants from four sites had analyzable 3D MRSI datasets acquired on Philips, GE or Siemens scanners at either 1.5T or 3T. MRSI data were analyzed using LCModel to quantify metabolites N-acetylaspartate (NAA), creatine (Cr), choline (Cho), and lactate (Lac). Receiver operating characteristic curves for NAA/Cho, Cho/Cr, lactate/Cr, and lactate/NAA were constructed for overall survival at 1-year (OS-1) and 6-month progression free survival (PFS-6). The OS-1 for the 17 evaluable patients was 59% (10/17). Receiver operating characteristic analyses found the NAA/Cho in tumor (AUC = 0.83, 95% CI: 0.61 to 1.00) and in peritumoral regions (AUC = 0.95, 95% CI 0.85 to 1.00) were predictive for survival at 1 year. PFS-6 was 65% (11/17). Neither NAA/Cho nor Cho/Cr was effective in predicting 6-month progression free survival. Lac/Cr in tumor was a significant negative predictor of PFS-6, indicating that higher lactate/Cr levels are associated with poorer outcome. (AUC = 0.79, 95% CI: 0.54 to 1.00). In conclusion, despite the small sample size in the setting of a multi-center trial comprising different vendors, field strengths, and varying levels of expertise at data acquisition, MRS markers NAA/Cho, Lac/Cr and Lac/NAA predicted overall survival at 1 year and 6-month progression free survival. This study validates that MRSI may be useful in evaluating the prognosis in glioblastoma and should be considered for incorporating into multi-center clinical trials.

Amyloid positron emission tomography (PET) imaging with florbetapir ¹⁸F (¹⁸F-AV-45) allows in vivo assessment of cerebral amyloid load and can be used in the evaluation of progression of Alzheimer's disease (AD) and other dementias associated with b-amyloid. However, cortical amyloid deposition can occur in healthy cases, as well as in patients with AD and quantification of cortical amyloid burden can improve the ¹⁸F-AV-45 PET imaging evaluations. The quantification is mostly performed by cortical-to-cerebellum standardized uptake value ratio (SUVr). The aim of our study was to compare two methods for SUVr calculations in amyloid florbetapir ¹⁸F PET brain imaging. In amyloid florbetapir ¹⁸F PET brain imaging study, we imaged 42 cases with the mean age of 72.6 ± 9.9 (mean ± standard deviation). They were imaged on different PET/computed tomography systems with 369.0 ± 34.2 kBq of ¹⁸F florbetapir. Data were reconstructed using the vendor's reconstruction software. Corresponding magnetic resonance imaging (MRI) data were retrieved, and matched PET and MRI data were transferred to a common platform. Two methods were used for the calculation of the ratio of cortical-to-cerebellar signal (SUVr). One method was based on the MIM Software Inc., Version 6.4 software and only uses PET data. The second approach used the PMOD Neuro tool (version 3.5). This approach utilizes PET and corresponding MRI data (preferably T1-weighted) for better brain segmentation. For all the 42 cases, the average SUVr values for MIM and PMOD applications were 1.24 ± 0.26 and 1.22 ± 0.25, respectively, with a mean difference of 0.02 ± 0.15. The repeatability coefficient was 0.15 (12.3% of the mean). The Spearman's rank correlation coefficient was very high, r = 0.96. For amyloid-negative cases, the average SUVr values were lower than all group SUVr average values, 0.96 ± 0.07 and 1.00 ± 0.09, for MIM and PMOD applications, respectively. A mean difference was 0.04 ± 0.12, the repeatability coefficient was 0.12 (12.9% of the mean) and the Spearman's rank correlation coefficient was modest, r = 0.55. For amyloid-positive patients, the average SUVr values were higher than the same all group values, 1.34 ± 0.16 and 1.35 ± 0.20, respectively, with a mean difference of 0.01 ± 0.16. The repeatability coefficient was 0.16 (11.9% of the mean). The Spearman's rank correlation coefficient was high, r = 0.93. Our results indicated that the SUVr values derived using MIM and PMOD Neuro are effectively interchangeable and well correlated. However, PET template-based quantification (MIM approach) is clinically friendlier and easier to use. MRI template-based quantification (PMOD Neuro) better delineates different regions of the brain, can be used with any tracer, and therefore is more suitable for research.

INTRODUCTION/BACKGROUND:The successful management of infected pelvic pressure ulcer patients (PPUP) depends on the distinction between infections limited to soft tissue (STI) and those with underlying osteomyelitis (OM), which can be difficult to determine clinically. Dual-isotope (DI) comprehensive imaging has excellent accuracy in localizing diabetic foot infection and differentiating OM from STI with SPECT/CT utilization. In this study, we assess the accuracy and confidence of the different DI SPECT/CT imaging steps in PPUP with confirmed diagnoses. PATIENTS AND METHODS/METHODS:Pelvic flow and blood pool imaging were followed by labeled white blood cell reinjection and Tc-99m hydroxymethylene-diphosphonate bone (bone scan) and In-111-leukocytes (white blood cell scan) DI planar and SPECT/CT (step 1) acquisitions. Tc-99m sulfur colloid (bone marrow scan)/WBCS SPECT/CT (step 2) images were obtained on the following day. DI step 1 planar, step 1 SPECT/CT, step 2 SPECT/CT, and combined step 1/step 2 SPECT/CT were reviewed separately for diagnosis and diagnosis confidence. The final diagnosis was confirmed by culture/pathology in 21 patients and clinical/imaging follow-up in 12 patients. RESULTS:There were 19 OM patients, three STI patients, and 11 patients with no infection. The final diagnosis agreement to DI combined step 1/step 2 SPECT/CT was higher than DI step 2 or step 1 SPECT/CT alone, or DI step 1 planar, as assessed by λ and error reduction %, respectively. Combined DI step 1/step 2 SPECT/CT was more sensitive than DI step 2 SPECT/CT and more specific than DI step 1 SPECT/CT, and showed higher diagnostic confidence than both imaging techniques. CONCLUSION/CONCLUSIONS:DI SPECT/CT is highly useful in evaluating PPUP with suspected infection. DI step 1 is more sensitive, whereas step 2 is more specific. Both step 1 and step 2 DI SPECT/CT images are needed to accurately and confidently assess for infection and distinguish OM from STI, which are crucial for optimal management.

An exploratory analysis of 75 follicular lymphoma patients treated with obinutuzumab or rituximab induction therapy (IT) for 4 weeks in the phase II GAUSS study aimed to determine whether positron emission tomography (PET) results could predict progression-free survival (PFS) and tumor response. The proportion of patients with a PFS event (progression or death) was higher in those who were PET-positive after IT (assessed using Deauville five-point scale criteria; 35/52, 67%) than PET-negative (5/20, 25%); the hazard ratio for progression or death was 0.25 (95%CI: 0.01-0.64; p = 0.0018). A significant association was also found when PET results were assessed using International Harmonization Project and European Organisation for Research and Treatment of Cancer criteria. Change between baseline and end of IT in values of standardized uptake value and other PET parameters were associated with PFS and response. Validation of these results in prospective studies of larger cohorts is warranted.