Jason J.S. Lee

Total Marrow Irradiation with Helical Tomotherapy for Bone Marrow Transplantation of Multiple Myeloma: First Experience in Asia

Three Asian patients with plasma cell myeloma stage IIIa with IgG predominant were selected for autologous hematopoietic cell transplantation (HSCT). Total marrow irradiation (TMI) tomotherapy planned with melphalan 140 mg/m2 as a preconditioning regimen of HSCT. Two image sets of computed tomography (CT) were scanned with 2.5 mm and 5 mm for the upper and lower part of the plan, respectively. The junction was determined and marked at 15 cm above knee on both thighs for upper and lower part of the plan. The clinical target volume (CTV) included the entire skeletal system. The planning target volume (PTV) was generated with with 0.8 cm for CTVextremities and with 0.5 cm margin for all other bones of CTV. A total dose of 800 cGy (200 cGy/fraction) was delivered to the PTV. Update to presentation, all of three patients post transplant without evidence of active disease were noted. During TMI treatment, one with grade 1 vomiting, two with grade 1 nausea, one with grade 1 mucositis, and three with grade 1 anorexia were noted. Toxicity of treatment was scored according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0). The average for upper part versus lower part of PTVBone marrow of CI and H-index were 1.5 and 1.4 versus 1.2 and 1.2, respectively. The dose reduction of TMI tomotherapy to various OARs of head, chest, and abdomen relative to TBI varied from 31% to 74%, 21% to 51%, and 46% to 63%, respectively. The maximum average value of registration for upper torso versus lower extremities in different translation directions were 5.1 mm versus 4.1 mm for pretreatment and 1.5 mm versus 0.7 mm for post-treatment, respectively. The average treatment time for the upper versus lower part in beam-on time, setup time, and MVCT registration time took roughly 49.9, 23.3, and 11.7 min versus 11.5, 10.0, and 7.3 min, respectively. The margin of PTV could be less than 1 cm under good fixation and close position confirmation with MVCT. Antiemetics should be prescribed in the whole course of TMI for emesis prevention. TMI technique replaced TBI technique with 8 Gy as conditioning regiment for multiple myeloma could be acceptable for the Asian and the outcomes were feasible for the Asian.

Toward Quantitative Small Animal Pinhole SPECT: Assessment of Quantitation Accuracy Prior to Image Compensations

PurposeWe assessed the quantitation accuracy of small animal pinhole single photon emission computed tomography (SPECT) under the current preclinical settings, where image compensations are not routinely applied.ProceduresThe effects of several common image-degrading factors and imaging parameters on quantitation accuracy were evaluated using Monte-Carlo simulation methods. Typical preclinical imaging configurations were modeled, and quantitative analyses were performed based on image reconstructions without compensating for attenuation, scatter, and limited system resolution.ResultsUsing mouse-sized phantom studies as examples, attenuation effects alone degraded quantitation accuracy by up to −18% (Tc-99m or In-111) or −41% (I-125). The inclusion of scatter effects changed the above numbers to −12% (Tc-99m or In-111) and −21% (I-125), respectively, indicating the significance of scatter in quantitative I-125 imaging. Region-of-interest (ROI) definitions have greater impacts on regional quantitation accuracy for small sphere sources as compared to attenuation and scatter effects. For the same ROI, SPECT acquisitions using pinhole apertures of different sizes could significantly affect the outcome, whereas the use of different radii-of-rotation yielded negligible differences in quantitation accuracy for the imaging configurations simulated.ConclusionsWe have systematically quantified the influence of several factors affecting the quantitation accuracy of small animal pinhole SPECT. In order to consistently achieve accurate quantitation within 5% of the truth, comprehensive image compensation methods are needed.

A positron emission tomography/computed tomography (PET/CT) acquisition protocol for CT radiation dose optimization.

BackgroundIn current combined positron emission tomography/computed tomography (PET/CT) systems, high-quality CT images not only increase diagnostic value by providing anatomic delineation of hyper- and hypometabolic tissues, but also shorten the acquisition time for attenuation correction compared with standard PET imaging. However, this technique potentially introduces more radiation burden to patients as a result of the higher radiation exposure from CT. MethodsIn this study, the radiation doses delivered from typical germanium-based and CT-based transmission scans were measured and compared using an anthropomorphic Rando Alderson phantom with insertions of thermoluminescent dosimeters. Image geometric distortion and quantified uptake values in PET images with different manipulating CT acquisition protocols for attenuation correction were also evaluated. ResultsIt was found that radiation doses during germanium-based transmission scans were almost negligible, while doses from CT-based transmission scans were significantly higher. Using a lower radiation dose, the CT acquisition protocol did not significantly affect attenuation correction and anatomic delineation in PET. ConclusionsThis study revealed the relation between image information and dose. The current PET/CT imaging acquisition protocol was improved by decreasing the radiation risks without sacrificing the diagnostic values

Integration of SimSET photon history generator in GATE for efficient Monte Carlo simulations of pinhole SPECT

The authors developed and validated an efficient Monte Carlo simulation (MCS) workflow to facilitate small animal pinhole SPECT imaging research. This workflow seamlessly integrates two existing MCS tools: simulation system for emission tomography (SimSET) and GEANT4 application for emission tomography (GATE). Specifically, we retained the strength of GATE in describing complex collimator/detector configurations to meet the anticipated needs for studying advanced pinhole collimation (e.g., multipinhole) geometry, while inserting the fast SimSET photon history generator (PHG) to circumvent the relatively slow GEANT4 MCS code used by GATE in simulating photon interactions inside voxelized phantoms. For validation, data generated from this new SimSET-GATE workflow were compared with those from GATE-only simulations as well as experimental measurements obtained using a commercial small animal pinhole SPECT system. Our results showed excellent agreement (e.g., in system point response functions and energy spectra) between SimSET-GATE and GATE-only simulations, and, more importantly, a significant computational speedup (up to ∼10-fold) provided by the new workflow. Satisfactory agreement between MCS results and experimental data were also observed. In conclusion, the authors have successfully integrated SimSET photon history generator in GATE for fast and realistic pinhole SPECT simulations, which can facilitate research in, for example, the development and application of quantitative pinhole and multipinhole SPECT for small animal imaging. This integrated simulation tool can also be adapted for studying other preclinical and clinical SPECT techniques.

Effects of long-term practice and task complexity on brain activities when performing abacus-based mental calculations: a PET study

PurposeThe aim of this study was to examine the neural bases for the exceptional mental calculation ability possessed by Chinese abacus experts through PET imaging.MethodsWe compared the different regional cerebral blood flow (rCBF) patterns using 15O-water PET in 10 abacus experts and 12 non-experts while they were performing each of the following three tasks: covert reading, simple addition, and complex contiguous addition. All data collected were analyzed using SPM2 and MNI templates.ResultsFor non-experts during the tasks of simple addition, the observed activation of brain regions were associated with coordination of language (inferior frontal network) and visuospatial processing (left parietal/frontal network). Similar activation patterns but with a larger visuospatial processing involvement were observed during complex contiguous addition tasks, suggesting the recruitment of more visuospatial memory for solving the complex problems. For abacus experts, however, the brain activation patterns showed slight differences when they were performing simple and complex addition tasks, both of which involve visuospatial processing (bilateral parietal/frontal network). These findings supported the notion that the experts were completing all the calculation process on a virtual mental abacus and relying on this same computational strategy in both simple and complex tasks, which required almost no increasing brain workload for solving the latter.ConclusionIn conclusion, after intensive training and practice, the neural pathways in an abacus expert have been connected more effectively for performing the number encoding and retrieval that are required in abacus tasks, resulting in exceptional mental computational ability.

Evaluating geometric accuracy of multi-platform stereotactic neuroimaging in radiosurgery.

We used a spherical phantom to evaluate geometric accuracy in multi-platform stereotactic neuroimaging for radiosurgery. The phantom consisted of two plastic 16-cm-diameter hemispheres in which an exchangeable 8-cm plastic functional cube was incorporated. The functional cube contained cylinder and point targets. The targets were filled with a mixed aqueous solution of 2-mM copper sulfate and 300-mg/ml iodinated contrast medium and were visible on both MR and X-ray images. Two MR scanners and a biplane X-ray angio-suite were used to scan the phantom stereotactically in two sessions of the experiment. The angio-suite was equipped with digital subtraction and distortion-correction software. The resulting stereotactic images were transferred to a dose-planning computer for length measurement and coordinate determination of the targets. The mean errors of the measured cylinder length on distortion non-corrected X-ray stereotactic images were 0.24 ± 0.14 and 0.73 ± 0.10 mm, respectively, in the experiments; on distortion-corrected images 0.22 ± 0.10 and 0.35 ± 0.39 mm. They were 0.50 ± 0.24, 0.25 ± 0.19 and 0.49 ± 0.34, 0.23 ± 0.25 mm, respectively, of the two MR scanners. The mean errors of coordinate determination of point targets between the stereotactic MR and the distortion-corrected X-ray images were 0.70 ± 0.18, 0.52 ± 0.22 and 0.76 ± 0.25, 0.40 ± 0.10 mm, respectively, in the experiments. We found that the overall geometric errors of target delineation between stereotactic MR and X-ray images were in the submillimeter range. The current study validates the multi-platform and multi-facility stereotactic neuroimaging practice and ensures imaging accuracy in radiosurgery.

Dynamic evaluation of absorbed dose to the bladder wall with a balloon-bladder phantom during a study using [18F]fluorodeoxyglucose positron emission imaging

An accurate evaluation of the absorbed dose to the bladder wall from 2-[18F]fluoro-2-deoxy-d-glucose (FDG) is clinically important because the bladder is considered as a critical organ in most positron emission tomography (PET) studies that cumulate about 20% of the total activity injection during image procedures. In the MIRD calculation, no allowance is made for the inclusion of all the dynamic parameters that affect the actual dose to the bladder wall to be taken in the dose assessment. The goal of the study is to propose a dose evaluation model by using a dynamic bladder phantom and time-activity curves from the bladder PET imaging. The proposed model takes all dynamic parameters into account and provides a much more accurate dose estimation to the bladder. In this study, the lowest dose to the bladder wall was obtained at the conditions of having a larger initial volume for the bladder contents and a higher production rate for urine. It is then advised patients to drink a bulk amount of water before the FDG injection or after urine voiding to facilitate urine production and to enlarge the bladder surface area, which are the most crucial steps in reducing the dose to the bladder wall. In our study, the voiding schedule in dose calculation plays certain roles although it is much more critical in the conventional MIRD calculation. The model estimated that the lowest dose to the bladder would occur at an initial void about 40 min after the FDG injection and the urine voiding was as complete as possible.

Monte Carlo simulation of a GE eXplore VISTA system for quantitative small animal PET imaging.

ObjectiveWe aim to establish an evaluation platform for the GE eXplore VISTA small animal positron emission tomography (PET) scanner, a dual layer phoswich system, by using Monte Carlo simulation. MethodsWe developed a detection model based on the Geant4 Application for Tomographic Emission to realistically reproduce the physics of PET, the scanner configuration, and the data collecting system of an eXplore VISTA system. For verification purpose, several different physical phantoms were simulated to perform evaluation tests, including sensitivity, spatial resolution, scatter fraction, and count rate performance, which were compared with an actual scanner. After the experimental validation, our detection model was applied to assess the quantification loss in the reconstructed images associated with photon attenuation, photon scatter, and random coincidences. ResultsA simulated sensitivity profile as a function of 18F point source axial position was fitted to the measured results. In terms of spatial resolution, agreement was within 10–18% for the point source at various locations. The simulated and measured scatter fractions differed by less than 4.3 and 5.2% for the physical mouse and rat phantoms, respectively. The count rate performance of our model was matched by the measured results, up to the peak activity concentration of 455 kBq/ml for the mouse-sized phantom and 141 kBq/ml for the rat-sized phantom. Finally, we found that photon attenuation is the dominant physical degrading factor in quantitative analysis (>13.4%). ConclusionThese results suggested that the proposed detection model is able to produce realistic data from the eXplore VISTA system with knowing the ground truth, thus facilitating its evaluation for small animal PET studies.

Merging molecular and anatomical information: a feasibility study on rodents using microPET and MRI.

ObjectiveThe use of the micro positron emission tomography (microPET) technique provides a powerful means for molecular imaging on small animals, while its inferior spatial resolution offers insufficient anatomical information which impedes the interpretations of the scans. To improve this limitation, it often relies on a clinical magnetic resonance imaging (MRI) for providing anatomical details. In this study, we designed and developed a new image co-registration platform which contains a stereotactic frame and external fiducial markers for microPET and MRI studies. The image co-registration accuracies were also validated by this new platform using various imaging protocols for microPET and MRI. MethodsThe microPET images were reconstructed by filtered back-projection (FBP) and ordered subset expectation maximization (OSEM) methods. Two MRI pulse sequences, two-dimensional T1-weighted fast spin-echo (FSE) and three-dimensional spoiled gradient recalled (SPGR), were employed in the studies. Two MRI scanning protocols were proposed for small animal imaging: the whole-body high-speed mode and the partial high-resolution mode. ResultsReconstructed images from two different modalities were integrated by point-to-point registration via the external fiducials. Four inter-modality matched co-registration pairs (FBP–FSE, FBP–SPGR, OSEM–FSE, OSEM–SPGR) were obtained for both the high speed and high resolution modes. Co-registration accuracy was given as the average fiducial registration error (FRE) between the centroids of six markers from the registered images. The overall systemic FREs were about 0.50 mm. ConclusionsFrom the inter-modality FRE comparison, MRI imaging with FSE performed better than that with SPGR sequence, due to its higher signal-to-noise ratio and less magnetic susceptibility effects. In the microPET perspective, the OSEM was superior to the FBP, as a result of fewer image artifacts.

Evaluation of the dose to the bladder wall using a dynamic balloon-bladder phantom and TLD measurements in 18F-FDG PET studies.

[18F]-2-deoxyglucose (18F-FDG) is one of the most useful radiopharmaceuticals in clinical positron emission tomographic imaging. Its final metabolic destination is the bladder, which accumulates the highest absorbed dose in the body during imaging. The aims of this study were to develop a dynamic bladder phantom to emulate the dynamic response of the bladder and to evaluate changes in the dose to the bladder wall during the imaging procedure. 18F-FDG of various concentrations can be drip-fed intravenously to the balloon-bladder at different uptake phases or extracted from the phantom during voiding. A dose evaluation model, introducing the concept of photon energy flux conversion into the dose calculation, is thus developed for clinical evaluation. The dose to the bladder wall using the proposed model is comparable to that measured using a thermoluminescence dosimeter (TLD), with a less than 5% discrepancy. The main advantages of the model are the use of the dose conversion factor, phi TLD, which is determined from real TLD measurements, and the ability to consider the dynamic characteristics of the bladder. To overcome the problems of diverse dose distributions among subjects, time-activity information provided by clinical bladder imaging is required, so that the method can be applied to other radiopharmaceuticals.