Aaron B. Brill

MIRD Pamphlet No. 23: Quantitative SPECT for Patient-Specific 3-Dimensional Dosimetry in Internal Radionuclide Therapy

In internal radionuclide therapy, a growing interest in voxel-level estimates of tissue-absorbed dose has been driven by the desire to report radiobiologic quantities that account for the biologic consequences of both spatial and temporal nonuniformities in these dose estimates. This report presents an overview of 3-dimensional SPECT methods and requirements for internal dosimetry at both regional and voxel levels. Combined SPECT/CT image-based methods are emphasized, because the CT-derived anatomic information allows one to address multiple technical factors that affect SPECT quantification while facilitating the patient-specific voxel-level dosimetry calculation itself. SPECT imaging and reconstruction techniques for quantification in radionuclide therapy are not necessarily the same as those designed to optimize diagnostic imaging quality. The current overview is intended as an introduction to an upcoming series of MIRD pamphlets with detailed radionuclide-specific recommendations intended to provide best-practice SPECT quantification–based guidance for radionuclide dosimetry.

A Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident: Objectives, Design and Methods

Abstract Chornobyl Thyroid Diseases Study Group of Belarus, Ukraine, and the USA. A Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident: Objectives, Design and Methods. Radiat. Res. 161, 481–492 (2004). The thyroid gland in children is one of the organs that is most sensitive to external exposure to X and γ rays. However, data on the risk of thyroid cancer in children after exposure to radioactive iodines are sparse. The Chornobyl accident in Ukraine in 1986 led to the exposure of large populations to radioactive iodines, particularly 131I. This paper describes an ongoing cohort study being conducted in Belarus and Ukraine that includes 25,161 subjects under the age of 18 years in 1986 who are being screened for thyroid diseases every 2 years. Individual thyroid doses are being estimated for all study subjects based on measurement of the radioactivity of the thyroid gland made in 1986 together with a radioecological model and interview data. Approximately 100 histologically confirmed thyroid cancers were detected as a consequence of the first round of screening. The data will enable fitting appropriate dose–response models, which are important in both radiation epidemiology and public health for prediction of risks from exposure to radioactive iodines from medical sources and any future nuclear accidents. Plans are to continue to follow-up the cohort for at least three screening cycles, which will lead to more precise estimates of risk.

Elastic Moduli of Thyroid Tissues under Compression

The aim of this study was to evaluate the elastic moduli of thyroid tissues under uniaxial compression and to establish the biomechanical fundamentals for accurate interpretation of thyroid elastograms. A total of 67 thyroid samples (24 samples of normal thyroid tissue, 2 samples of thyroid tissue with chronic thyroiditis, 12 samples of adenomatous goiter lesions and 7 samples of follicular adenoma, 19 samples of papillary adenocarcinoma (PAC) and 3 samples of follicular adenocarcinoma (FAC)) obtained from 36 patients who had received thyroid surgery were subjected to biomechanical testing within three hours after surgical resection at precompression strains of 5%, 10% and 20% and applied strains of 1%, 2%, 5% and 10% of sample height. As a result, the mean values of elastic moduli for benign thyroid lesions at all examined precompression levels were significantly higher than those for normal thyroid tissue measured at the same load (p<0.01). At low precompression (5%) and compression (1–2%) levels, benign thyroid nodule samples were 1.7 times harder than normal thyroid tissue. At high precompression (20%) and compression (10%) levels, this difference increased to 2.4 times. Stiffness of PAC samples was significantly higher than those for normal thyroid tissue and benign thyroid tumors measured at the same load (p<0.01). At low precompression (5%) and compression (1–2%) levels, PAC samples were 5.0 times harder than normal thyroid tissue. At high precompression (20%) and compression (10%) levels, this difference increased to 17.7 times. In contrast, samples of FAC were much softer than PAC (p<0.05) and were comparable in stiffness to normal thyroid tissues. The significant differences in the stiffness between normal thyroid tissue and thyroid tumors may provide useful information for accurate interpretation of thyroid elastograms.

Accelerated SPECT Monte Carlo Simulation using Multiple Projection Sampling and Convolution-based Forced Detection

Monte Carlo (MC) is a well-utilized tool for simulating photon transport in single photon emission computed tomography (SPECT) due to its ability to accurately model physical processes of photon transport. As a consequence of this accuracy, it suffers from a relatively low detection efficiency and long computation time. One technique used to improve the speed of MC modeling is the effective and well-established variance reduction technique (VRT) known as forced detection (FD). With this method, photons are followed as they traverse the object under study but are then forced to travel in the direction of the detector surface, whereby they are detected at a single detector location. Another method, called convolution-based forced detection (CFD), is based on the fundamental idea of FD with the exception that detected photons are detected at multiple detector locations and determined with a distance-dependent blurring kernel. In order to further increase the speed of MC, a method named multiple projection convolution-based forced detection (MP-CFD) is presented. Rather than forcing photons to hit a single detector, the MP-CFD method follows the photon transport through the object but then, at each scatter site, forces the photon to interact with a number of detectors at a variety of angles surrounding the object. This way, it is possible to simulate all the projection images of a SPECT simulation in parallel, rather than as independent projections. The result of this is vastly improved simulation time as much of the computation load of simulating photon transport through the object is done only once for all projection angles. The results of the proposed MP-CFD method agrees well with the experimental data in measurements of point spread function (PSF), producing a correlation coefficient (r2) of 0.99 compared to experimental data. The speed of MP-CFD is shown to be about 60 times faster than a regular forced detection MC program with similar results.

Changes in Radiation Dose with Variations in Human Anatomy: Moderately and Severely Obese Adults

The phantoms used in standardized dose assessment are based on a median (i.e., 50th percentile) individual of a large population, for example, adult males or females or children of a particular age. Here we describe phantoms that model instead the influence of obesity on specific absorbed fractions (SAFs) and dose factors in adults. Methods: The literature was reviewed to evaluate how individual organ sizes change with variations in body weight in mildly and severely obese adult men and women. On the basis of the literature evaluation, changes were made to our deformable reference adult male and female total-body models. Monte Carlo simulations of radiation transport were performed. SAFs for photons were generated for mildly and severely obese adults, and comparisons were made to the reference (50th) percentile SAF values. Results: SAFs studied between the obese phantoms and the 50th percentile reference phantoms were not significantly different from the reference 50th percentile individual, with the exception of intestines irradiating some abdominal organs, because of an increase in separation between folds caused by an increase in mesenteric adipose deposits. Some low-energy values for certain organ pairs were different, possibly due only to the statistical variability of the data at these low energies. Conclusion: The effect of obesity on dose calculations for internal emitters is minor and may be neglected in the routine use of standardized dose estimates.

USE OF RADIOPHARMACEUTICALS IN DIAGNOSTIC NUCLEAR MEDICINE IN THE UNITED STATES: 1960–2010

AbstractTo reconstruct reliable nuclear medicine-related occupational radiation doses or doses received as patients from radiopharmaceuticals over the last five decades, the authors assessed which radiopharmaceuticals were used in different time periods, their relative frequency of use, and typical values of the administered activity. This paper presents data on the changing patterns of clinical use of radiopharmaceuticals and documents the range of activity administered to adult patients undergoing diagnostic nuclear medicine procedures in the U.S. between 1960 and 2010. Data are presented for 15 diagnostic imaging procedures that include thyroid scan and thyroid uptake; brain scan; brain blood flow; lung perfusion and ventilation; bone, liver, hepatobiliary, bone marrow, pancreas, and kidney scans; cardiac imaging procedures; tumor localization studies; localization of gastrointestinal bleeding; and non-imaging studies of blood volume and iron metabolism. Data on the relative use of radiopharmaceuticals were collected using key informant interviews and comprehensive literature reviews of typical administered activities of these diagnostic nuclear medicine studies. Responses of key informants on relative use of radiopharmaceuticals are in agreement with published literature. Results of this study will be used for retrospective reconstruction of occupational and personal medical radiation doses from diagnostic radiopharmaceuticals to members of the U.S. radiologic technologists’ cohort and in reconstructing radiation doses from occupational or patient radiation exposures to other U.S. workers or patient populations.

Cancer and circulatory disease risks in US radiologic technologists associated with performing procedures involving radionuclides

Objectives The number of nuclear medicine procedures has increased substantially over the past several decades, with uncertain health risks to the medical workers who perform them. We estimated risks of incidence and mortality from cancer and circulatory disease associated with performing procedures involving the use of radionuclides. Methods From a nationwide cohort of 90 955 US radiologic technologists who completed a mailed questionnaire during 1994–1998, 22 039 reported ever performing diagnostic radionuclide procedures, brachytherapy, radioactive iodine therapy, or other radionuclide therapy. We calculated multivariable-adjusted HRs and 95% CIs for incidence (through 2003–2005) and mortality (through 2008) associated with performing these procedures. Results Ever (versus never) performing radionuclide procedures was not associated with risks for most end points examined. However, we observed increased risks for squamous cell carcinoma of the skin (HR=1.29, 95% CI 1.01 to 1.66) with ever performing diagnostic radionuclide procedures, for myocardial infarction incidence (HR=1.37, 95% CI 1.10 to 1.70), all-cause mortality (HR=1.10, 95% CI 1.00 to 1.20) and all-cancer mortality (HR=1.20, 95% CI 1.01 to 1.43) with ever performing brachytherapy, and for mortality from all causes (HR=1.14, 95% CI 1.01 to 1.30), breast cancer (HR=2.68, 95% CI 1.10 to 6.51), and myocardial infarction (HR=1.76, 95% CI 1.02 to 3.04) with ever performing other radionuclide therapy procedures (excluding brachytherapy and radioactive iodine); increasing risks were also observed with greater frequency of performing these procedures, particularly before 1980. Conclusions The modest health risks among radiologic technologists performing procedures using radionuclides require further examination in studies with individual dose estimates, more detailed information regarding types of procedures performed and radionuclides used, and longer follow-up.

Nuclear medicine practices in the 1950s through the mid-1970s and occupational radiation doses to technologists from diagnostic radioisotope procedures.

AbstractData on occupational radiation exposure from nuclear medicine procedures for the time period of the 1950s through the 1970s is important for retrospective health risk studies of medical personnel who conducted those activities. However, limited information is available on occupational exposure received by physicians and technologists who performed nuclear medicine procedures during those years. To better understand and characterize historical radiation exposures to technologists, the authors collected information on nuclear medicine practices in the 1950s, 1960s, and 1970s. To collect historical data needed to reconstruct doses to technologists, a focus group interview was held with experts who began using radioisotopes in medicine in the 1950s and the 1960s. Typical protocols and descriptions of clinical practices of diagnostic radioisotope procedures were defined by the focus group and were used to estimate occupational doses received by personnel, per nuclear medicine procedure, conducted in the 1950s to 1960s using radiopharmaceuticals available at that time. The radionuclide activities in the organs of the reference patient were calculated using the biokinetic models described in ICRP Publication 53. Air kerma rates as a function of distance from a reference patient were calculated by Monte Carlo radiation transport calculations using a hybrid computational phantom. Estimates of occupational doses to nuclear medicine technologists per procedure were found to vary from less than 0.01 &mgr;Sv (thyroid scan with 1.85 MBq of administered 131I-iodide) to 0.4 &mgr;Sv (brain scan with 26 MBq of 203Hg-chlormerodin). Occupational doses for the same diagnostic procedures starting in the mid-1960s but using 99mTc were also estimated. The doses estimated in this study show that the introduction of 99mTc resulted in an increase in occupational doses per procedure.

Vertex detection in a stack of Si-drift detectors for high resolution gamma-ray imaging

Usually the position resolution in imaging applications with gamma rays is limited due to the range of secondary reaction products to a few mm. Here a new approach will be presented using the vertex of the gamma interaction as the quantity for position measurement. Because the dominant interaction is the Compton effect the vertex detection method as used in particle physics needs a number of essential modifications. Therefore a detector system is investigated consisting of a stack of Si-drift detectors for the vertex detection of the first Compton interaction and a secondary absorption detector where the position of the scattered photon is detected. A number of effects and possible solutions will be discussed including depth of interaction measurement and track reconstruction of the Compton electron which yields useful information. Another very promising approach of measuring the track projection as in a TPC (time projection chamber) will be presented including first successful measurements in a gas detector. Because the expected rate in the first and second detector is of the order of 1 MHz and 10 MHz respectively the concept of read out electronics and data processing based on VLSI custom chips for signal shaping and first buffering and digital pipe-line processors based on FPGA s is presented. Finally a full system for small animal imaging based on the principle of a Compton Camera will be discussed in terms of achievable resolution and sensitivity.

Organ Dose Estimates for Hyperthyroid Patients Treated with 131I: An Update of the Thyrotoxicosis Follow-Up Study

The Thyrotoxicosis Therapy Follow-up Study (TTFUS) is comprised of 35,593 hyperthyroid patients treated from the mid-1940s through the mid-1960s. One objective of the TTFUS was to evaluate the long-term effects of high-dose iodine-131 (131I) treatment (1–4). In the TTFUS cohort, 23,020 patients were treated with 131I, including 21,536 patients with Graves disease (GD), 1,203 patients with toxic nodular goiter (TNG) and 281 patients with unknown disease. The study population constituted the largest group of hyperthyroid patients ever examined in a single health risk study. The average number (±1 standard deviation) of 131I treatments per patient was 1.7 ± 1.4 for the GD patients and 2.1 ± 2.1 for the TNG patients. The average total 131I administered activity was 380 ± 360 MBq for GD patients and 640 ± 550 MBq for TNG patients. In this work, a biokinetic model for iodine was developed to derive organ residence times and to reconstruct the radiation-absorbed doses to the thyroid gland and to other organs resulting from administration of 131I to hyperthyroid patients. Based on 131I data for a small, kinetically well-characterized sub-cohort of patients, multivariate regression equations were developed to relate the numbers of disintegrations of 131I in more than 50 organs and tissues to anatomical (thyroid mass) and clinical (percentage thyroid uptake and pulse rate) parameters. These equations were then applied to estimate the numbers of 131I disintegrations in the organs and tissues of all other hyperthyroid patients in the TTFUS who were treated with 131I. The reference voxel phantoms adopted by the International Commission on Radiological Protection (ICRP) were then used to calculate the absorbed doses in more than 20 organs and tissues of the body. As expected, the absorbed doses were found to be highest in the thyroid (arithmetic means of 120 and 140 Gy for GD and TNG patients, respectively). Absorbed doses in organs other than the thyroid were much smaller, with arithmetic means of 1.6 Gy, 1.5 Gy and 0.65 Gy for esophagus, thymus and salivary glands, respectively. The arithmetic mean doses to all other organs and tissues were more than 100 times less than those to the thyroid gland. To our knowledge, this work represents the most comprehensive study to date of the doses received by persons treated with 131I for hyperthyroidism.