Jianguo Qian

SPECT-CT system for small animal imaging

The Detector Group at the Thomas Jefferson National Accelerator Facility (Jefferson Lab) and the Biology, Physics, and Applied Sciences Departments at the College of William and Mary are collaborating on the development of a miniature dual modality SPECT-CT system for mouse imaging. The detector heads of the SPECT sub-system are designed to be capable of imaging the gamma- and X-ray emissions (28-35 keV) of the radioactive isotope iodine-125 (I-125). Two different sets of I-125 imaging detectors are configured on a gantry that has an open-barrel type design. One set of detector heads is based on the 1-in square Hamamatsu R5900-M64 position sensitive photomultiplier tube coupled to crystal scintillator arrays. The other detector heads configured on the gantry are two 5-in diameter Hamamatsu R3292-based compact gamma cameras. The X-ray radiographic projections are obtained using a LIXI Inc. model LF-85-503-OS X-ray imaging system that has an active area of 5.5 cm in diameter. The open-barrel shaped gantry facilitates the positioning of various mini gamma-ray imaging detectors and the X-ray system. The data acquisition and gantry control is interfaced through a Macintosh G3 workstation. Preliminary SPECT reconstruction results using the R5900 based detector are presented.

Improved compressed sensing-based cone-beam CT reconstruction using adaptive prior image constraints

Volumetric cone-beam CT (CBCT) images are acquired repeatedly during a course of radiation therapy and a natural question to ask is whether CBCT images obtained earlier in the process can be utilized as prior knowledge to reduce patient imaging dose in subsequent scans. The purpose of this work is to develop an adaptive prior image constrained compressed sensing (APICCS) method to solve this problem. Reconstructed images using full projections are taken on the first day of radiation therapy treatment and are used as prior images. The subsequent scans are acquired using a protocol of sparse projections. In the proposed APICCS algorithm, the prior images are utilized as an initial guess and are incorporated into the objective function in the compressed sensing (CS)-based iterative reconstruction process. Furthermore, the prior information is employed to detect any possible mismatched regions between the prior and current images for improved reconstruction. For this purpose, the prior images and the reconstructed images are classified into three anatomical regions: air, soft tissue and bone. Mismatched regions are identified by local differences of the corresponding groups in the two classified sets of images. A distance transformation is then introduced to convert the information into an adaptive voxel-dependent relaxation map. In constructing the relaxation map, the matched regions (unchanged anatomy) between the prior and current images are assigned with smaller weight values, which are translated into less influence on the CS iterative reconstruction process. On the other hand, the mismatched regions (changed anatomy) are associated with larger values and the regions are updated more by the new projection data, thus avoiding any possible adverse effects of prior images. The APICCS approach was systematically assessed by using patient data acquired under standard and low-dose protocols for qualitative and quantitative comparisons. The APICCS method provides an effective way for us to enhance the image quality at the matched regions between the prior and current images compared to the existing PICCS algorithm. Compared to the current CBCT imaging protocols, the APICCS algorithm allows an imaging dose reduction of 10-40 times due to the greatly reduced number of projections and lower x-ray tube current level coming from the low-dose protocol.

Dose reconstruction for volumetric modulated arc therapy (VMAT) using cone-beam CT and dynamic log files

Volumetric modulated arc therapy (VMAT) has recently emerged as a new clinical modality for conformal radiation therapy. The aim of this work is to establish a methodology and procedure for retrospectively reconstructing the actual dose delivered in VMAT based on the pre-treatment cone-beam computed tomography (CBCT) and dynamic log files. CBCT was performed before the dose delivery and the systems log files were retrieved after the delivery. Actual delivery at a control point including MLC leaf positions, gantry angles and cumulative monitor units (MUs) was recorded in the log files and the information was extracted using in-house developed software. The extracted information was then embedded into the original treatment DICOM-radiation therapy (RT) file to replace the original control point parameters. This reconstituted DICOM-RT file was imported into the Eclipse treatment planning system (TPS) and dose was computed on the corresponding CBCT. A series of phantom experiments was performed to show the feasibility of dose reconstruction, validate the procedure and demonstrate the efficacy of this methodology. The resultant dose distributions and dose-volume histograms (DVHs) were compared with those of the original treatment plan. The studies indicated that CBCT-based VMAT dose reconstruction is readily achievable and provides a valuable tool for monitoring the dose actually delivered to the tumor target as well as the sensitive structures. In the absence of setup errors, the reconstructed dose shows no significant difference from the original pCT-based plan. It is also elucidated that the proposed method is capable of revealing the dosimetric changes in the presence of setup errors. The method reported here affords an objective means for dosimetric evaluation of VMAT delivery and is useful for adaptive VMAT in future.

First Demonstration of Multiplexed X-Ray Fluorescence Computed Tomography (XFCT) Imaging

Simultaneous imaging of multiple probes or biomarkers represents a critical step toward high specificity molecular imaging. In this work, we propose to utilize the element-specific nature of the X-ray fluorescence (XRF) signal for imaging multiple elements simultaneously (multiplexing) using XRF computed tomography (XFCT). A 5-mm-diameter pencil beam produced by a polychromatic X-ray source (150 kV, 20 mA) was used to stimulate emission of XRF photons from 2% (weight/volume) gold (Au), gadolinium (Gd), and barium (Ba) embedded within a water phantom. The phantom was translated and rotated relative to the stationary pencil beam in a first-generation CT geometry. The X-ray energy spectrum was collected for 18 s at each position using a cadmium telluride detector. The spectra were then used to isolate the K shell XRF peak and to generate sinograms for the three elements of interest. The distribution and concentration of the three elements were reconstructed with the iterative maximum likelihood expectation maximization algorithm. The linearity between the XFCT intensity and the concentrations of elements of interest was investigated. We found that measured XRF spectra showed sharp peaks characteristic of Au, Gd, and Ba. The narrow full-width at half-maximum (FWHM) of the peaks strongly supports the potential of XFCT for multiplexed imaging of Au, Gd, and Ba (FWHMAu,Kα1 = 0.619 keV, FWHMAu,Kα2=1.371 keV , FWHMGd,Kα=1.297 keV, FWHMGd,Kβ=0.974 keV , FWHMBa,Kα=0.852 keV, and FWHMBa,Kβ=0.594 keV ). The distribution of Au, Gd, and Ba in the water phantom was clearly identifiable in the reconstructed XRF images. Our results showed linear relationships between the XRF intensity of each tested element and their concentrations (R2Au=0.944 , RGd2=0.986, and RBa2=0.999), suggesting that XFCT is capable of quantitative imaging. Finally, a transmission CT image was obtained to show the potential of the approach for providing attenuation correction and morphological information. In conclusion, XFCT is a promising modality for multiplexed imaging of high atomic number probes.

Dose verification for respiratory-gated volumetric modulated arc therapy.

A novel commercial medical linac system (TrueBeam™, Varian Medical Systems, Palo Alto, CA) allows respiratory-gated volumetric modulated arc therapy (VMAT), a new modality for treating moving tumors with high precision and improved accuracy by allowing for regular motion associated with a patients breathing during VMAT delivery. The purpose of this work is to adapt a previously-developed dose reconstruction technique to evaluate the fidelity of VMAT treatment during gated delivery under clinic-relevant periodic motion related to patient breathing. A Varian TrueBeam system was used in this study. VMAT plans were created for three patients with lung or pancreas tumors. Conventional 6 and 15 MV beams with flattening filter and high-dose-rate 10 MV beams with no flattening filter were used in these plans. Each patient plan was delivered to a phantom first without gating and then with gating for three simulated respiratory periods (3, 4.5 and 6 s). Using the adapted log-file-based dose reconstruction procedure supplemented with ion chamber array (Seven29™, PTW, Freiburg, Germany) measurements, the delivered dose was used to evaluate the fidelity of gated VMAT delivery. Comparison of Seven29 measurements with and without gating showed good agreement with gamma-index passing rates above 99% for 1%/1 mm dose accuracy/distance-to-agreement criteria. With original plans as reference, gamma-index passing rates were 100% for the reconstituted plans (1%/1 mm criteria) and 93.5-100% for gated Seven29 measurements (3%/3 mm criteria). In the presence of leaf error deliberately introduced into the gated delivery of a pancreas patient plan, both dose reconstruction and Seven29 measurement consistently indicated substantial dosimetric differences from the original plan. In summary, a dose reconstruction procedure was demonstrated for evaluating the accuracy of respiratory-gated VMAT delivery. This technique showed that under clinical operation, the TrueBeam system faithfully realized treatment plans with gated delivery. This methodology affords a useful tool for machine- and patient-specific quality assurance of the newly available respiratory-gated VMAT.

A compact gamma camera for biological imaging

A compact detector, sized particularly for imaging a mouse, is described. The active area of the detector is approximately 46 mm /spl times/ 96 mm. Two flat-panel Hamamatsu H8500 position-sensitive photomultiplier tubes (PSPMTs) are coupled to a pixellated NaI(Tl) scintillator which views the animal through a copper-beryllium (CuBe) parallel-hole collimator specially designed for /sup 125/I. Although the PSPMTs have insensitive areas at their edges and there is a physical gap, corrections for scintillation light collection at the junction between the two tubes results in a uniform response across the entire rectangular area of the detector. The system described has been developed to optimize both sensitivity and resolution for in-vivo imaging of small animals injected with iodinated compounds. We demonstrate an in-vivo application of this detector, particularly to SPECT, by imaging mice injected with approximately 10-15 /spl mu/Ci of /sup 125/I.

Development of XFCT imaging strategy for monitoring the spatial distribution of platinum-based chemodrugs: Instrumentation and phantom validation

PURPOSE Developing an imaging method to directly monitor the spatial distribution of platinum-based (Pt) drugs at the tumor region is of critical importance for early assessment of treatment efficacy and personalized treatment. In this study, the authors investigated the feasibility of imaging platinum (Pt)-based drug distribution using x-ray fluorescence (XRF, a.k.a. characteristic x ray) CT (XFCT). METHODS A 5-mm-diameter pencil beam produced by a polychromatic x-ray source equipped with a tungsten anode was used to stimulate emission of XRF photons from Pt drug embedded within a water phantom. The phantom was translated and rotated relative to the stationary pencil beam in a first-generation CT geometry. The x-ray energy spectrum was collected for 18 s at each position using a cadmium telluride detector. The spectra were then used for the K-shell XRF peak isolation and sinogram generation for Pt. The distribution and concentration of Pt were reconstructed with an iterative maximum likelihood expectation maximization algorithm. The capability of XFCT to multiplexed imaging of Pt, gadolinium (Gd), and iodine (I) within a water phantom was also investigated. RESULTS Measured XRF spectrum showed a sharp peak characteristic of Pt with a narrow full-width at half-maximum (FWHM) (FWHMKα1 = 1.138 keV, FWHMKα2 = 1.052 keV). The distribution of Pt drug in the water phantom was clearly identifiable on the reconstructed XRF images. Our results showed a linear relationship between the XRF intensity of Pt and its concentrations (R(2) = 0.995), suggesting that XFCT is capable of quantitative imaging. A transmission CT image was also obtained to show the potential of the approach for providing attenuation correction and morphological information. Finally, the distribution of Pt, Gd, and I in the water phantom was clearly identifiable in the reconstructed images from XFCT multiplexed imaging. CONCLUSIONS XFCT is a promising modality for monitoring the spatial distribution of Pt drugs. The technique may be useful in tailoring tumor treatment regimen in the future.

Clinical development of a failure detection-based online repositioning strategy for prostate IMRT—Experiments, simulation, and dosimetry study

PURPOSE To implement and evaluate clinic-ready adaptive imaging protocols for online patient repositioning (motion tracking) during prostate IMRT using treatment beam imaging supplemented by minimal, as-needed use of on-board kV. METHODS The authors examine the two-step decision-making strategy: (1) Use cine-MV imaging and online-updated characterization of prostate motion to detect target motion that is potentially beyond a predefined threshold and (2) use paired MV-kV 3D localization to determine overthreshold displacement and, if needed, reposition the patient. Two levels of clinical implementation were evaluated: (1) Field-by-field based motion correction for present-day linacs and (2) instantaneous repositioning for new-generation linacs with capabilities of simultaneous MV-kV imaging and remote automatic couch control during treatment delivery. Experiments were performed on a Varian Trilogy linac in clinical mode using a 4D motion phantom programed with prostate motion trajectories taken from patient data. Dosimetric impact was examined using a 2D ion chamber array. Simulations were done for 536 trajectories from 17 patients. RESULTS Despite the loss of marker detection efficiency caused by the MLC leaves sometimes obscuring the field at the markers projected position on the MV imager, the field-by-field correction halved (from 23% to 10%) the mean percentage of time that target displacement exceeded a 3 mm threshold, as compared to no intervention. This was achieved at minimal cost in additional imaging (average of one MV-kV pair per two to three treatment fractions) and with a very small number of repositionings (once every four to five fractions). Also with low kV usage (∼2/fraction), the instantaneous repositioning approach reduced overthreshold time by more than 75% (23% to 5%) even with severe MLC blockage as often encountered in current IMRT and could reduce the overthreshold time tenfold (to <2%) if the MLC blockage problem were relieved. The information acquired for repositioning using combined MV-kV images was found to have submillimeter accuracy. CONCLUSIONS This work demonstrated with a current clinical setup that substantial reduction of adverse targeting effects of intrafraction prostate motion can be realized. The proposed adaptive imaging strategy incurs minimal imaging dose to the patient as compared to other stereoscopic imaging techniques.

An economical dual-modality small animal imaging system with application to studies of diabetes

We have developed an economical dual-modality nuclear imaging system comprised of two Hamamatsu 125 mm diameter position sensitive photomultiplier tubes (PSPMT) viewing pixelated scintillators and a small fluoroscopic X-ray system (Lixi, Inc.). Collimators placed between the animal and the scintillators can be readily interchanged and include CuBe parallel-hole collimators with a range of resolution/sensitivity combinations as well as brass pinhole collimators with various pinhole diameters. The small X-ray fluoroscope provides 5 cm diameter images, several of which can readily be combined to provide structural information from the animal under study. The system has been used to follow the metabolism of compounds tagged with /sup 125/I. Biological information has been obtained on the uptake of tagged insulin and tumor necrosis factor-alpha (TNF/spl alpha/) thus demonstrating the applicability of this system for in vivo analysis of diseases such as diabetes.

A gamma camera re-evaluation of potassium iodide blocking efficiency in mice.

The protection of the thyroid against radioiodine uptake has been an important safety concern for decades. After several studies examined potassium iodide blockade efficacy in the 1960’s and 1970’s, a standard dosage was prescribed by both the World Health Organization and the U.S. Food and Drug Administration. In this paper, we tested the effectiveness of a scaled version of that standard dosage in comparison to higher doses in mice. A novel gamma camera was employed with a high spatial resolution for precisely quantifying activity within the thyroid and a field of view large enough to image the entire mouse body. Thyroid and whole-body 125I biodistribution was analyzed immediately after exposure and 1 and 7 days later. It was found that 1 h after exposure five times the scaled human dose blocked thyroid uptake about 40% more effectively than the 1X scaled dose. Even after 1 d and 7 d, five times the recommended scaled human dose blocked approximately 10% more effectively than the 1X dose. These data suggest the need for continued evaluation of the effectiveness of KI as a blocking agent and the application of novel, non-invasive technologies to this important human health issue.