James R. Galt

Technical aspects of myocardial spect imaging with technetium-99m sestamibi

Most reports to date using single photon emission computed tomography (SPECT) with technetium-99m (Tc-99m) sestamibi have used acquisition parameters that were optimized for thallium-201. To fully utilize the superior imaging characteristics of Tc-99m sestamibi, there is a need to optimize the technical aspects of SPECT imaging for this agent. Performance can be enhanced through the careful selection of optimal radiopharmaceutical doses, imaging sequences, acquisition parameters, reconstruction filters, perfusion quantification methods and multidimensional methods for visualizing perfusion distribution. The current report describes theoretical considerations, phantom studies and preliminary patient results that have led to optimized protocols, developed at Emory University and Cedars-Sinai Medical Center, for same-day rest-stress studies, given existing instrumentation and recommended dose limits. The optimizations were designed to fit a low-dose-high-dose rest-stress same-day imaging protocol. A principal change in the acquisition parameters compared with previous Tc-99m sestamibi protocols is the use of a high-resolution collimator. The approach is being developed in both prone and supine positions. A new method for extracting a 3-dimensional myocardial count distribution has been developed that uses spherical coordinates to sample the apical region and cylindrical coordinates to sample the rest of the myocardium. New methods for visualizing the myocardial distribution in multiple dimensions are also described, with improved 2-dimensional, as well as 3- and 4-dimensional (3 dimensions plus time) displays. In the improved 2-dimensional display, distance-weighted and volume-weighted polar maps are used that appear to significantly improve the representation of defect location and defect extent, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 Improves Stress and Rest Myocardial Perfusion Abnormalities in Patients With Severe Symptomatic Chronic Coronary Artery Disease

BackgroundWe report the effects of the administration of recombinant fibroblast growth factor-2 (rFGF-2) protein on myocardial perfusion using single photon emission computed tomography imaging in humans with advanced coronary disease. Methods and ResultsA total of 59 patients with coronary disease that was not amenable to mechanical revascularization underwent intracoronary (n=45) or intravenous (n=14) administration of rFGF-2 in ascending doses. Changes in perfusion were evaluated at baseline and again at 29, 57, and 180 days after rFGF-2 administration. In this uncontrolled study, perfusion scans were analyzed by 2 observers who were blinded to patient identity and test sequence; scans were displayed in random order, with scans from nonstudy patients randomly interspersed to enhance blinding. Combining all dose groups, a reduction occurred in the per-segment reversibility score (reflecting the magnitude of inducible ischemia) from 1.7±0.4 at baseline to 1.1±0.6 at day 29 (P <0.001), 1.2±0.7 at day 57 (P <0.001), and 1.1±0.7 at day 180 (P <0.001). The 37 patients with evidence of resting hypoperfusion had evidence of improved resting perfusion: their per-segment rest perfusion score of 1.5±0.5 at baseline decreased to 1.0±0.8 at day 29 (P <0.001), 1.0±0.8 at day 57 (P =0.003), and 1.1±0.9 at day 180 (P =0.11). ConclusionsThese preliminary data suggest that the administration of rFGF-2 to patients with advanced coronary disease resulted in an attenuation of stress-induced ischemia and an improvement in resting myocardial perfusion; these findings are consistent with a favorable effect of therapeutic angiogenesis.

CD34+ cell infusion after ST elevation myocardial infarction is associated with improved perfusion and is dose dependent

BACKGROUND the objective of the study was to determine whether the effects of infarct-related artery (IRA) infusion of autologous bone marrow-derived CD34(+) cells after ST elevation myocardial infarction (STEMI) are dependent on the dose (quantity and mobility) of the cells infused. Beneficial effects of IRA infusion of mononuclear cells after STEMI have been inconsistent, possibly because of differences in timing, cell type, quantity, and mobility of infused cells. METHODS patients were randomized to bone marrow harvest (n = 16) or control (n = 15). At a median of 8.3 days after coronary stenting for STEMI, CD34(+) cells were infused via the IRA at 3 dose levels (5, 10, and 15 × 10(6)) in cohorts of 5 patients each. Baseline and follow-up imaging and ex vivo CD34(+) cell mobility were performed. RESULTS Cell harvest and infusion were safe. Quantitative rest hypoperfusion score measured by single-photon emission computed tomography improved at 6 months in the ≥ 10 million cohorts compared with controls (-256 vs +14, P = .02). There was a trend toward improved ejection fraction at 6 months (+4.5%) in the ≥ 10 million cohorts compared with no change in the controls and 5 million cohort (+0.7%). Improved perfusion and infarct size reduction correlated with the quantity and mobility of the infused CD34(+) cells. CONCLUSIONS the effects of CD34(+) cell IRA infusion during the repair phase after STEMI are dose dependent and, at a threshold dose of 10 million CD34(+) cells, associated with a significant improvement in perfusion that may limit deterioration in cardiac function (IRA infusion of CD34(+) cells in patients with acute myocardial infarction [AMR-01] NCT00313339).

Extramedullary acute myeloid leukemia and the use of FDG-PET/CT.

Abstract: Extramedullary acute myeloid leukemia (AML) is a leukemic infiltration outside the bone marrow and is common in monocytic and myelomonocytic leukemia. The incidence is rare (0.6%-7.4%) and the clinical diagnosis requires a high index of suspicion. Fluorodeoxyglucose-positron emission tomography (FDG-PET) is used to detect, stage, and restage solid tumors, including lymphomas and Richter transformation. However its role in the management of liquid tumors and specifically in extramedullary AML has not been assessed. We present a case of a 64-year-old man who was diagnosed with AML and subsequently had recurrent extramedullary AML relapses. This case demonstrates the usefulness of FDG-PET for staging and assessment of the treatment response.

Spectrum of FDG PET/CT findings in Burkitt lymphoma.

Purpose: F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) is known to be a useful diagnostic tool for staging, restaging, and monitoring therapy for lymphoma. The purpose of this retrospective study is to present a spectrum of FDG PET findings at initial presentation of Burkitt lymphoma and subsequent findings after therapy. Method and Materials: We retrospectively reviewed 48 patients with Burkitt lymphoma referred for a total of 160 FDG PET/computed tomography (CT) scans at our institution. We characterized the disease distribution of Burkitt lymphoma in all patients and measured representative FDG activity from initial staging scans. Therapeutic response and disease remission were assessed in patients with PET/CT and clinical follow-up studies. Results: Of the 48 patients diagnosed with Burkitt lymphoma, 25 patients had FDG PET/CT scans for initial staging. All untreated lesions of Burkitt lymphoma were highly FDG avid. The mean maximum standardized uptake value of 54 representative lesions is 16.5 (range: 6–54). Twelve patients were immune compromised. The majority of patients had disease localized to the abdomen and the pelvis. Extranodal involvement was identified in more than half of the patients studied. Conclusion: The American (or sporadic) form of Burkitt lymphoma presented with intense hypermetabolic lesions when untreated. The information is useful in evaluating post-treatment studies in the absence of a pretreatment scan.

A Simple Method for Estimating Dose Delivered to Hepatocellular Carcinoma after Yttrium-90 Glass-Based Radioembolization Therapy: Preliminary Results of a Proof of Concept Study

PURPOSE To investigate a simple semiquantitative method to estimate yttrium-90 ((90)Y) dose delivered with radioembolization to infiltrative hepatocellular carcinoma (HCC). MATERIALS AND METHODS In a prospective study, patients with infiltrative HCC and portal vein thrombosis (PVT) underwent glass-based (90)Y radioembolization including technetium-99m macroaggregated albumin ((99m)Tc-MAA) hepatopulmonary shunt study before therapy and bremsstrahlung single photon emission computed tomography (SPECT)/computed tomography (CT) after (90)Y radioembolization. Baseline magnetic resonance imaging was coregistered with (99m)Tc-MAA and bremsstrahlung SPECT/CT imaging separately. Unit tumor activity ((90)Y radioactivity delivered to each cubic centimeter of tumor) was estimated based on a lobar infusion approach. Correlation between proportions of (99m)Tc-MAA and (90)Y delivered to the tumor was investigated. Survival analysis was performed using Kaplan-Meier estimations. RESULTS (90)Y therapy was administered in 18 consecutive patients (median age, 55.3 y; mean tumor volume, 588 cm(3)). Higher intratumoral (90)Y dose predicted prolonged survival, with 13.2-month median survival in patients with HCC and mean (90)Y dose of ≥ 100 Gy versus 4.6-month median survival for other patients (P < .001). Of administered (90)Y dose, 51.9% was delivered to the targeted tumors compared with 74.1% of (99m)Tc-MAA with linear correlation between biodistribution of (99m)Tc-MAA and (90)Y observed (Pearson r = 0.774, P < .001). CONCLUSIONS The findings in this study suggest that approximately 50% of administered (90)Y dose is taken up by targeted infiltrative HCC with PVT. Intratumoral (90)Y dose ≥ 100 Gy in unresectable infiltrative HCC via a lobar intraarterial approach is a positive prognostic factor for survival.

Improved quantification in 123I cardiac SPECT imaging with deconvolution of septal penetration.

Objectives123I is becoming an important radionuclide for cardiac imaging. Multiple, low-abundance, high-energy photons associated with 123I imaging can cause septal penetration in the collimators and degrade quantification of the 123I cardiac uptake. This study presents a method for the deconvolution of septal penetration (DSP) for improving quantification in 123I cardiac single photon emission computed tomography (SPECT). MethodsDistance-dependent point spread functions were measured for low-energy high-resolution collimators on a dual-head SPECT system. The measured point spread functions were used in two-dimensional (2-D) and three-dimensional (3-D) models of the collimator response, respectively. 2-D DSP and 3-D DSP were then developed and implemented using iterative reconstruction. A cardiac torso phantom with an internal calibration source was designed with various heart-to-calibration ratios (HCRs) simulating different levels of a patients uptake. SPECT acquisitions of the phantom were performed using optimized acquisition and processing parameters for 123I cardiac SPECT. HCRs were calculated using planar projection and tomographic reconstructions. The paired t-test and regression analysis were used to compare the HCRs given by different calculation methods. ResultsSPECT produced more accurate HCRs than planar imaging. The slopes of the regression lines for SPECT using filtered back-projection were statistically significantly higher than those for planar imaging (0.2118±0.0297 vs. 0.0819±0.0070, P=0.0001). 2-D DSP and 3-D DSP yielded similar HCRs that were close to the true HCR. The slopes of the regression lines for 2-D DSP and 3-D DSP were 0.9203±0.0523 and 0.9101±0.0304, respectively. The DSP HCRs were significantly more accurate than those calculated without DSP (P<0.0001). ConclusionDSP significantly improves quantification in 123I cardiac SPECT imaging. 2-D DSP with its less computational burden shows promise for implementation in clinical practice so as to allow the use of the widely available low-energy, high-resolution collimators for quantitative 123I cardiac SPECT imaging.

Quantitative Dosimetry for Yttrium-90 Radionuclide Therapy: Tumor Dose Predicts Fluorodeoxyglucose Positron Emission Tomography Response in Hepatic Metastatic Melanoma

PURPOSE To assess a new method for generating patient-specific volumetric dose calculations and analyze the relationship between tumor dose and positron emission tomography (PET) response after radioembolization of hepatic melanoma metastases. METHODS AND MATERIALS Yttrium-90 ((90)Y) bremsstrahlung single photon emission computed tomography (SPECT)/computed tomography (CT) acquired after (90)Y radioembolization was convolved with published (90)Y Monte Carlo estimated dose deposition kernels to create a three-dimensional dose distribution. Dose-volume histograms were calculated for tumor volumes manually defined from magnetic resonance imaging or PET/CT imaging. Tumor response was assessed by absolute reduction in maximum standardized uptake value (SUV(max)) and total lesion glycolysis (TLG). RESULTS Seven patients with 30 tumors treated with (90)Y for hepatic metastatic melanoma with available (90)Y SPECT/CT and PET/CT before and after treatment were identified for analysis. The median (range) for minimum, mean, and maximum dose per tumor volume was 16.9 Gy (5.7-43.5 Gy), 28.6 Gy (13.8-65.6 Gy) and 36.6 Gy (20-124 Gy), respectively. Response was assessed by fluorodeoxyglucose PET/CT at a median time after treatment of 2.8 months (range, 1.2-7.9 months). Mean tumor dose (P = .03) and the percentage of tumor volume receiving ≥ 50 Gy (P < .01) significantly predicted for decrease in tumor SUV(max), whereas maximum tumor dose predicted for decrease in tumor TLG (P < .01). CONCLUSIONS Volumetric dose calculations showed a statistically significant association with metabolic tumor response. The significant dose-response relationship points to the clinical utility of patient-specific absorbed dose calculations for radionuclide therapy.

Attenuation and scatter compensation in myocardial perfusion SPECT.

Nonuniform attenuation, Compton scatter, and limited, spatially varying resolution degrade both the qualitative and quantitative nature of myocardial perfusion SPECT. Physicians must recognize and understand the effects of these factors on myocardial perfusion SPECT for optimal interpretation and use of this important imaging technique. Recent developments in the design and implementation of compensation algorithms and transmission-based imaging promise to provide clinically realistic solutions to these effects and provide the framework for truly quantitative imaging. This achievement should improve the diagnostic accuracy and cost-effectiveness of myocardial perfusion SPECT.

Do 18F-FDG PET/CT parameters in oropharyngeal and oral cavity squamous cell carcinomas indicate HPV status?

Objective The aim of this study was to explore the relationship of PET/CT parameters with human papillomavirus (HPV) status of oropharyngeal (OP) and oral cavity (OC) squamous cell carcinomas (SCCs). Patients and Methods We retrospectively reviewed 39 patients with OC and OP-SCC who underwent staging 18F-FDG PET/CT. PET/CT parameters were measured for the primary tumor and the hottest involved node, including SUVmax, SUVmean, SUVpeak, metabolic tumor volume, total lesion glycolysis, standardized added metabolic activity (SAM), and normalized SAM. Patient characteristics were compared between HPV positive (HPV+) and negative (HPV−) groups. Receiver operating characteristic analysis was used to dichotomize PET/CT parameters into high and low. Logistic regression models predicting HPV status were fit for each PET/CT parameter. Results The HPV+ group was composed of 18 patients all with OP-SCC; the HPV− group consisted of 21 patients, 4 OP cancer patients and 17 OC cancer patients. The HPV+ group had a higher proportion of N2 stage (94% vs 43%; P < 0.001). Nodal PET/CT parameters were higher in the HPV+ group (P < 0.01); this difference was not present for the primary lesion. After adjusting for sex and age, the association of higher nodal SUVmax (odds ratio [OR], 9.67), SUVmean (OR, 10.48), SUVpeak (OR 9.67), metabolic tumor volume (OR, 14.52), total lesion glycolysis (OR, 11.84), and SAM, normalized SAM (OR, 16.21) with HPV+ status remained statistically significant (P < 0.05). Conclusions Nodal PET/CT parameters predict HPV status. High nodal FDG uptake should raise suspicion for positive HPV status in the evaluation of the primary lesion.