Carole Schreck

Mapping of Lymphatic Drainage from the Prostate Using Filtered 99mTc-Sulfur Nanocolloid and SPECT/CT

We have developed a practice procedure for prostate lymphoscintigraphy using SPECT/CT and filtered 99mTc-sulfur nanocolloid, as an alternative to the proprietary product 99mTc-Nanocoll, which is not approved in the United States. Methods: Ten patients were enrolled for this study, and all received radiotracer prepared using a 100-nm membrane filter at a commercial radiopharmacy. Whole-body scans and SPECT/CT studies were performed within 1.5–3 h after the radiotracer had been administered directly into 6 locations of the prostate gland under transrectal ultrasound guidance. The radiation dose was estimated from the first 3 patients. Lymphatic drainage mapping was performed, and lymph nodes were identified. Results: The estimated radiation dose ranged from 3.9 to 5.2 mSv/MBq. The locations of lymph nodes draining the prostate gland were similar to those found using the proprietary product. Conclusion: When the proprietary radiolabeled nanocolloid indicated for lymphoscintigraphy is not available, prostate lymph node mapping and identification are still feasible using filtered 99mTc-sulfur nanocolloid.

Inter-scanner differences in in vivo QCT measurements of the density and strength of the proximal femur remain after correction with anthropomorphic standardization phantoms

In multicenter studies and longitudinal studies that use two or more different quantitative computed tomography (QCT) imaging systems, anthropomorphic standardization phantoms (ASPs) are used to correct inter-scanner differences and allow pooling of data. In this study, in vivo imaging of 20 women on two imaging systems was used to evaluate inter-scanner differences in hip integral BMD (iBMD), trabecular BMD (tBMD), cortical BMD (cBMD), femoral neck yield moment (My) and yield force (Fy), and finite-element derived strength of the femur under stance (FEstance) and fall (FEfall) loading. Six different ASPs were used to derive inter-scanner correction equations. Significant (p<0.05) inter-scanner differences were detected in all measurements except My and FEfall, and no ASP-based correction was able to reduce inter-scanner variability to corresponding levels of intra-scanner precision. Inter-scanner variability was considerably higher than intra-scanner precision, even in cases where the mean inter-scanner difference was statistically insignificant. A significant (p<0.01) effect of body size on inter-scanner differences in BMD was detected, demonstrating a need to address the effects of body size on QCT measurements. The results of this study show that significant inter-scanner differences in QCT-based measurements of BMD and bone strength can remain even when using an ASP.

Quantitative accuracy of PET/CT for image‐based kinetic analysis

It is essential to achieve quantitative accuracy of radioactivity concentrations (Bq/ml) when performing compartmental modeling and kinetic analysis of dynamic sequences of reconstructed PET images. Dynamic PET data can be acquired in list mode, and often is preferred over frame mode acquisitions due to the flexibility of reformatting the list mode data into different dynamic image sequences after the acquisition is complete. However, most PET data is acquired as static frames. It therefore is important to evaluate the quantitative accuracy of list mode or dynamic PET acquisitions prior to their use for clinical or research applications. We evaluated the quantitative accuracy of list mode acquisitions obtained with a Siemens Biograph 16 PET/CT scanner at our institution; the image data were acquired from an anthropomorphic phantom (Data Spectrum, Hillsborough, NC) filled with an aqueous solution of 18F-fluorodeoxyglucose (FDG). PET data were acquired with the phantom for the following three different configurations: (1) with nonradioactive water in the body compartment, and aqueous solution of 18F-FDG only in a finable cylindrical insert to mimic the first few seconds of highly concentrated radioactivity within the field of view such as that in major venous or pulmonary vessels, or in the right or left cardiac ventricles, (2) with radioactivity throughout the entire body compartment and imaged within 3 min time frames in list mode, and (3) with radioactivity throughout the body compartment and imaged in list mode and reformatted into sequential time frames having intervals of 3, 10, 20, 30, 50, 67 sec, respectively (i.e., total of 180 sec). All measured concentration values were compared against values acquired from static images or against true values calculated from injected dose corrected for physical decay of 18F. These analyses demonstrated that the count rate limitation is minimal or negligible in general as long as there is no more than 370-440 MBq (10-12 mCi) radioactivity entirely within the axial FOV for 1 bed position required for dynamic PET, and the list mode acquisition provides quantitative radioactivity concentration values for all ranges of radioactivity levels. In addition, reformatting a single list mode acquisition into frame data having different time intervals retains quantitative accuracy with respect to static frame data and compared to the known radionuclide concentration in the phantom. Within these constraints, the list mode data acquired with the Biograph 16 PET/CT system is quantitatively accurate for image-based compartmental modeling and kinetic analysis.

Quantification of Changes in Skeletal Muscle Amino Acid Kinetics in Adult Humans in Response to Exercise via Positron-emission Tomography with L-[methyl-11C] methionine

Dynamic positron emission tomography (PET) imaging of with L-[methyl- 11 C]methionine (11C-MET) was developed in the late 1990’s to non-invasively estimate skeletal muscle protein synthesis, but no studies have shown that the measurements respond to resistance exercise, which stimulates protein synthesis in humans. Ten healthy women aged 25-75 years underwent a 14-hour fast, followed by unilateral knee extension and flexion exercise and consumption of an 8-ounce serving of fruit juice. Five subjects underwent dynamic 11C-MET PET imaging of the mid-thigh 2-3 hours after exercise and five were imaged 1 hour after exercise. Images were processed to obtain the Patlak slope K i , which describes the fractional extraction rate of 11C-MET into skeletal muscle protein. Additionally, the images were processed with a three-compartment kinetic model to determine rate constants for 11C-MET transport between muscle tissue, protein and plasma. All subjects showed excellent mid-thigh uptake of 11C-MET. Subjects imaged 2-3 hours after exercise showed no unilateral enhancement. However, subjects imaged one hour post-exercise showed an enhancement of 11C-MET uptake in the exercised leg compared to the control leg, corresponding to K i elevations between 3.8% - 31.1%. From the three-compartment analysis, the increased uptake corresponded primarily to an increased rate constant for extraction of 11C-MET from plasma to skeletal muscle tissue. Finally, older subjects tended to have smaller values of K i than the younger subjects. In summary, 11C-MET kinetics is responsive to a unilateral exercise stimulus, and this technique may prove useful to study skeletal muscle amino acid kinetics in response to exercise, aging and other conditions

Quantitative accuracy of PET for image-based kinetic analysis

Accuracy in quantification of activity concentrations (e.g., in Bq/ml) is essential for compartment modeling and kinetic analysis of dynamic reconstructed PET images. Dynamic PET data can be acquired in list-mode, and often are preferred over frame mode acquisitions due to the flexibility of reformatting the list-mode data into different dynamic image sequences after the acquisition is complete. However, most PET data are acquired as static frames. It therefore is important to evaluate the quantitative accuracy of list-mode or dynamic PET acquisitions prior to their use for clinical or research applications. The quantitative accuracy of list-mode acquisitions obtained with a Siemens Biograph 16 PET/CT scanner at our institution was evaluated; the image data were acquired from an anthropomorphic phantom (Data Spectrum, Hillsborough, NC) filled with an aqueous solution of 18F-fluorodeoxyglucose (FDG). PET data were acquired with the phantom for the following three different configurations: (1) with nonradioactive water in the body compartment and aqueous solution of 18F-FDG in only a fillable cylindrical insert to simulate the first several seconds of highly concentrated radioactivity within the field of view such as that in major venous or pulmonary vessels or in the cardiac ventricles, (2) with radioactivity throughout the entire body compartment and imaged with 3 min static frames and 12 min in list-mode that was reformatted into four 3-min frames, and (3) with radioactivity throughout the body compartment and imaged in list-mode and reformatted into sequential time frames having durations of 3, 10, 20, 30, 50, and 67 s, respectively (i.e., total of 180 s). All measured concentration values were compared against values acquired from static images or against the actual activity concentrations calculated from the calibrated activities dispensed into the phantom corrected for physical decay of 18F. These analyses demonstrated that the count rate limitation is minimal or negligible as long as there is no more than 370-440 MBq (10-12 mCi) activity entirely within the axial FOV and that list-mode acquisition yields accurate quantitation of activity concentrations over a clinically realistic range of activities. In addition, reformatting a single list-mode acquisition into frames of different durations retains quantitative accuracy with respect to static frame data and compared to the known radionuclide concentration in the phantom. Within these constraints, the list-mode data acquired with the Biograph 16 PET/CT system are quantitatively accurate for image-based kinetic analysis.

259 NOVEL SCINTIGRAPHIC PARAMETERS TO ASSESS LEFT VENTRICULAR DYSSYNCHRONY IN PATIENTS REQUIRING CARDIAC RESYNCHRONIZATION THERAPY.

Background The equilibrium radionuclide angiogram (ERNA) is an imaging method that can be used to assess left ventricular (LV) function and synchrony. Each pixel of an ERNA is defined by its phase (ø) and amplitude (Amp), which together define its vector; the Amp gives the vectors length. The vector sum of all Amps, based on the angular distribution of ø, divided by the scalar sum of the length of all the vectors defines a new parameter, synchrony (S). The degree of randomness or disorder in the LV based on the Shannon information measure normalized for the number of ø in the LV region defines another new parameter, entropy (E). With complete synchrony, S = 1 and E = 0; with complete dyssynchrony, S = 0 and E = 1. We evaluated S and E in patients requiring cardiac resynchronization therapy (CRT) to determine if these measures can be correlated with a clinical benefit from CRT. Methods We studied 14 patients (9 males, mean age 66 ± 15 years) with advanced congestive heart failure, LV ejection fraction (EF) ≤ 35% and QRS ≥ 120 ms. ERNA was performed before and within 10 weeks after CRT. Assessment of clinical status was made based on NYHA classification assessed before and within 10 weeks of CRT. Patients were graded 2 (n = 5), 1 (n = 5) or 0 (n = 4) if they improved 2, 1, or 0 NYHA classes, respectively. This was then correlated to changes in LVEF, SD ø, S, and E after CRT using a Pearson correlation. Results The patients classified 2 showed large improvements in S and E, less in SD of ø, and least in LVEF. S and E were best correlated with outcome and were strongest when combined (multiple R = .87). One patient classified 2 had improved S and E but not LVEF or SD ø. Most patients without clinical improvement, nonetheless, had an improved LVEF. Changes in LVEF or SD of ø could not differentiate among clinical groups. Conclusions S and E seem to measure different functional characteristics than LVEF. They show promise to be the best and most reproducibly correlated with functional status after CRT.

258 UTILITY OF EQUILIBRIUM RADIONUCLIDE ANGIOGRAMS TO GUIDE CORONARY SINUS LEAD PLACEMENT IN HEART FAILURE PATIENTS REQUIRING CARDIAC RESYNCHRONIZATION THERAPY.

Background In heart failure patients requiring cardiac resynchronization therapy (CRT), there is no reliable method to determine the optimal site to place the coronary sinus (CS) lead. The equilibrium radionuclide angiogram (ERNA) provides an assessment of left ventricular function and the location of dyssynchrony. We compared using the findings from ERNA to guide CS lead placement with the traditional method of placing the CS lead in a lateral CS branch to determine whether ERNA-guided placement improved response to CRT. Methods We obtained ERNA studies on 14 patients with NYHA Class III and IV heart failure referred for CRT device implantation or upgrade from a right-ventricular device. Each pixel of an ERNA is defined by its phase (ø) and amplitude (Amp), which together define its vector; the Amp gives the vectors length. The vector sum of all Amps, based on the angular distribution of ø, divided by the scalar sum of the length of all the vectors defines a new parameter, synchrony (S). With complete synchrony, S = 1, and with complete dyssynchrony, S = 0. Using ERNA studies obtained before and after CRT, we evaluated S, ejection fraction (EF), and NYHA Class at both times. Results 3 out of 6 patients who underwent traditional CS lead placement did not show any improvement in NYHA class (50%). 7 of the 8 patients who had ERNA-guided CS lead placement had an improvement in NYHA class (88%). More patients in the ERNA-guided group had clinical improvement as compared to the traditional group (p = .02 by chi-square analysis). One patient in the ERNA-guided group did not benefit since the location where the CS lead had been placed showed nonviable tissue by a subsequent PET scan. The degree of change in S also significantly predicted the clinical response to CRT. Conclusions In heart failure patients requiring CRT, ERNA is a novel method that can be used to assess dyssynchrony and guide CS lead placement. The use of this method resulted in significant improvements in NYHA class and S but not in EF. Given these findings, this is a novel technique that warrants further study.