This report describes recommended techniques for radiopharmaceutical biodistribution data acquisition and analysis in human subjects to estimate radiation absorbed dose using the Medical Internal Radiation Dose (MIRD) schema. The document has been prepared in a format to address two audiences: individuals with a primary interest in designing clinical trials who are not experts in dosimetry and individuals with extensive experience with dosimetry-based protocols and calculational methodology. For the first group, the general concepts involved in biodistribution data acquisition are presented, with guidance provided for the number of measurements (data points) required. For those with expertise in dosimetry, highlighted sections, examples and appendices have been included to provide calculational details, as well as references, for the techniques involved. This document is intended also to serve as a guide for the investigator in choosing the appropriate methodologies when acquiring and preparing product data for review by national regulatory agencies. The emphasis is on planar imaging techniques commonly available in most nuclear medicine departments and laboratories. The measurement of the biodistribution of radiopharmaceuticals is an important aspect in calculating absorbed dose from internally deposited radionuclides. Three phases are presented: data collection, data analysis and data processing. In the first phase, data collection, the identification of source regions, the determination of their appropriate temporal sampling and the acquisition of data are discussed. In the second phase, quantitative measurement techniques involving imaging by planar scintillation camera, SPECT and PET for the calculation of activity in source regions as a function of time are discussed. In addition, nonimaging measurement techniques, including external radiation monitoring, tissue-sample counting (blood and biopsy) and excreta counting are also considered. The third phase, data processing, involves curve-fitting techniques to integrate the source time-activity curves (determining the area under these curves). For some applications, compartmental modeling procedures may be used. Last, appendices are included that provide a table of symbols and definitions, a checklist for study protocol design, example formats for quantitative imaging protocols, temporal sampling error analysis techniques and selected calculational examples. The utilization of the presented approach should aid in the standardization of protocol design for collecting kinetic data and in the calculation of absorbed dose estimates.

https://jnm.snmjournals.org/content/jnumed/40/2/37S.full.pdf

MIRD pamphlet no. 16: Techniques for quantitative radiopharmaceutical biodistribution data acquisition and analysis for use in human radiation dose estimates.

On-board imager (OBI) based cone-beam computed tomography (CBCT) has become available in radiotherapy clinics to accurately identify the target in the treatment position. However, due to the relatively slow gantry rotation (typically about 60 s for a full 360° scan) in acquiring the CBCT projection data, the patient's respiratory motion causes serious problems such as blurring, doubling, streaking and distortion in the reconstructed images, which heavily degrade the image quality and the target localization. In this work, we present a motion compensation method for slow-rotating CBCT scans by incorporating into image reconstruction a patient-specific motion model, which is derived from previously obtained four-dimensional (4D) treatment planning CT images of the same patient via deformable registration. The registration of the 4D CT phases results in transformations representing a temporal sequence of three-dimensional (3D) deformation fields, or in other words, a 4D model of organ motion. The algorithm was developed heuristically in two-dimensional (2D) parallel-beam geometry and extended to 3D cone-beam geometry. By simulations with digital phantoms capable of translational motion and other complex motion, we demonstrated that the algorithm can reduce the motion artefacts locally, and restore the tumour size and shape, which may thereby improve the accuracy of target localization and patient positioning when CBCT is used as the treatment guidance.

http://iopscience.iop.org/article/10.1088/0031-9155/51/2/005/pdf

Motion correction for improved target localization with on-board cone-beam computed tomography

Attenuation compensation for cardiac single-photon emission computed tomographic imaging: Part 1. Impact of attenuation and methods of estimating attenuation maps

An iterative algorithm is presented for accelerated reconstruction of cone beam transmission CT data (CBCT). CBCT supplies an attenuation map for SPECT attenuation compensation and anatomical correlation. Iterative algorithms are necessary to reduce truncation artifacts and 3D reconstruction artifacts. An existing transmission maximum-likelihood algorithm (TRML) is accurate but the reconstruction time is too long. The new algorithm is a modified EM algorithm, based on ordered subsets (OSEM). OSEM was evaluated in comparison to TRML using a thorax phantom and a 3D Defrise phantom. A wide range of image measures were evaluated, including spatial resolution, noise, log likelihood, region quantification, truncation artifact removal, and 3D artifact removal. For appropriate subset size, OSEM produced essentially the same image as TRML, but required only one-tenth as many iterations. Thus, adequate images were available in two to four iterations (20-30 min on a SPARC 2 workstation). Further, OSEM still approximately maximizes likelihood: divergence occurs only for very high (and clinically irrelevant) iterations. Ordered subsets are likely to be useful in other geometries (fan and parallel) and for emission CT as well. Therefore, with ordered subsets, high-quality iterative reconstruction is now available in clinically practical reconstructions times.

https://iopscience.iop.org/article/10.1088/0031-9155/40/7/006/pdf

Transmission maximum-likelihood reconstruction with ordered subsets for cone beam CT.

Statistical methods for image reconstruction such as the maximum likelihood expectation maximization are more robust and flexible than analytical inversion methods and allow for accurate modelling of the counting statistics and photon transport during acquisition of projection data. Statistical reconstruction is prohibitively slow when applied to clinical x-ray CT due to the large data sets and the high number of iterations required for reconstructing high-resolution images. Recently, however, powerful methods for accelerating statistical reconstruction have been proposed which, instead of accessing all projections simultaneously for updating an image estimate, are based on accessing a subset of projections at the time during iterative reconstruction. In this paper we study images generated by the convex algorithm accelerated by the use of ordered subsets (the OS convex algorithm (OSC)) for data sets with sizes, noise levels and spatial resolution representative of x-ray CT imaging. It is only in the case of extremely high acceleration factors (higher than 50, corresponding to fewer than 20 projections per subset), that areas with incorrect grey values appear in the reconstructed images, and that image noise increases compared with the standard convex algorithm. These image degradations can be adequately corrected for by running the final iteration of OSC with a reduced number of subsets. Even by applying such a relatively slow final iteration, OSC produces almost an equal resolution and lesion contrast as the standard convex algorithm, but more than two orders of magnitude faster.

https://iopscience.iop.org/article/10.1088/0031-9155/46/7/307/pdf

Ordered subset reconstruction for x-ray CT

Radionuclide transmission CT generated on a rotating gamma camera can improve SPECT imaging by providing attenuation maps for attenuation compensation and for anatomical correlation. This paper demonstrates the feasibility and high quality of cone-beam transmission CT (CB-CT) of human subjects, in comparison to conventional parallel-ray CT, and evaluates some possible imaging protocols. Two CB-CT implementation modes, with a cone-beam collimator and without any collimator, were evaluated. Three human subjects of different dimensions were imaged. For the two smaller subjects, the CB-CT images were dramatically superior, in terms of noise and resolution, to those obtained with a parallel-ray geometry. The image noise was less by a factor of 6. CB-CT linear attenuation coefficients were found to be in close agreement with published values for various tissues. For the largest subject, image truncation produced a ring artifact at the edge, but inside the artifact, the image quality was still very good. Cone-beam images obtained without any collimator were acceptable, but photon scatter degraded the image contrast.

http://jnm.snmjournals.org/content/33/1/150.full.pdf

Imaging of the human torso using cone-beam transmission CT implemented on a rotating gamma camera.

This paper develops and tests cone-beam transmission computed tomography (CB-CT) for attenuation compensation of SPECT images. CB-CT was implemented on a rotating gamma camera with a point source (1-2 mCi) of 99mTc, and a light-weight aluminum source holder. A cone-beam collimator may be used but is not required. Since the point source is either located at the collimator focal point, or the camera is uncollimated, CB-CT has excellent sensitivity (at least 150 times that of a parallel-hole, high-resolution collimator). The predicted resolution is equal to the intrinsic gamma camera resolution (3-4 mm), which is much higher than for a high-resolution, parallel-hole collimator (10-20 mm). In the present study, CB-CT provided low noise, high-resolution attenuation maps for use in a nonuniform attenuation-weighted backprojection algorithm. The attenuation compensation accuracy was tested using basic geometries of line sources and nonuniform density models. For the appropriate scaling of the attenuation map, the attenuation compensation was accurate and removed the SPECT image distortion associated with nonuniform attenuation. Attenuation maps acquired either with cone beam collimator or without any collimator were both successful. Using CB-CT, SPECT can thus be made much more accurate without adding unduly to the imaging time, complexity, or cost.

https://jnm.snmjournals.org/content/jnumed/32/9/1813.full.pdf

D.A. Bassano

Papers

Imaging of the human torso using cone-beam transmission CT implemented on a rotating gamma camera.

Cone-beam transmission computed tomography for nonuniform attenuation compensation of SPECT images.