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1.  A heterogeneous human tissue mimicking phantom for RF heating and MRI thermal monitoring verification 
Physics in medicine and biology  2012;57(7):2021-2037.
This paper describes a heterogeneous phantom that mimics a human thigh with a deep seated tumor, for the purpose of studying the performance of radiofrequency (RF) heating equipment and non-invasive temperature monitoring with magnetic resonance imaging (MRI). The heterogeneous cylindrical phantom was constructed with an outer fat layer surrounding an inner core of phantom material mimicking muscle, tumor and marrow-filled bone. The component materials were formulated to have dielectric and thermal properties similar to human tissues. The dielectric properties of the tissue-mimicking phantom materials were measured with a microwave vector network analyzer and impedance probe over the frequency range of 80 – 500 MHz and at temperatures of 24°C, 37°C, and 45°C. The specific heat values of the component materials were measured using a differential scanning calorimeter over the temperature range of 15 – 55°C. The thermal conductivity value was obtained from fitting the curves obtained from one-dimensional heat transfer measurement. The phantom was used to verify the operation of a cylindrical 4-antenna annular phased array extremity applicator (140 MHz), by examining the proton resonance frequency shift (PRFS) thermal imaging patterns for various magnitude/phase settings (including settings to focus heating in tumor). For muscle and tumor materials, MR imaging was also used to measure T1/T2* values (1.5 Tesla) and to obtain the slope of the PRFS phase change vs. temperature change curve. The dielectric and thermal properties of the phantom materials were in close agreement to well-accepted published results for human tissues. The phantom was able to successfully demonstrate satisfactory operation of the tested heating equipment. The MRI-measured thermal distributions matched the expected patterns for various magnitude/phase settings of the applicator, allowing the phantom to be used as a quality assurance tool. Importantly, the material formulations for the various tissue types may be used to construct customized phantoms that are tailored for different anatomical sites.
PMCID: PMC3728669  PMID: 22430012
Tissue mimicking phantom; dielectric properties; thermal properties; T1/T2*; MR thermal imaging; hyperthermia; quality assurance
2.  Quantitative, Simultaneous PET/MRI for Intratumoral Imaging with an MRI-Compatible PET Scanner 
Noninvasive methods are needed to explore the heterogeneous tumor microenvironment and its modulation by therapy. Hybrid PET/MRI systems are being developed for small-animal and clinical use. The advantage of these integrated systems depends on their ability to provide MR images that are spatially coincident with simultaneously acquired PET images, allowing combined functional MRI and PET studies of intratissue heterogeneity. Although much effort has been devoted to developing this new technology, the issue of quantitative and spatial fidelity of PET images from hybrid PET/MRI systems to the tissues imaged has received little attention. Here, we evaluated the ability of a first-generation, small-animal MRI-compatible PET scanner to accurately depict heterogeneous patterns of radiotracer uptake in tumors.
Quantitative imaging characteristics of the MRI-compatible PET (PET/MRI) scanner were evaluated with phantoms using calibration coefficients derived from a mouse-sized linearity phantom. PET performance was compared with a commercial small-animal PET system and autoradiography in tumor-bearing mice. Pixel and structure-based similarity metrics were used to evaluate image concordance among modalities. Feasibility of simultaneous PET/MRI functional imaging of tumors was explored by following 64Cu-labeled antibody uptake in relation to diffusion MRI using cooccurrence matrix analysis.
The PET/MRI scanner showed stable and linear response. Activity concentration recovery values (measured and true activity concentration) calculated for 4-mm-diameter rods within linearity and uniform activity rod phantoms were near unity (0.97 ± 0.06 and 1.03 ± 0.03, respectively). Intratumoral uptake patterns for both 18F-FDG and a 64Cu-antibody acquired using the PET/MRI scanner and small-animal PET were highly correlated with autoradiography (r > 0.99) and with each other (r = 0.97 ± 0.01). On the basis of these data, we performed a preliminary study comparing diffusion MRI and radiolabeled antibody uptake patterns over time and visualized movement of antibodies from the vascular space into the tumor mass.
The MRI-compatible PET scanner provided tumor images that were quantitatively accurate and spatially concordant with autoradiography and the small-animal PET examination. Cooccurrence matrix approaches enabled effective analysis of multimodal image sets. These observations confirm the ability of the current simultaneous PET/MRI system to provide accurate observations of intratumoral function and serve as a benchmark for future evaluations of hybrid instrumentation.
PMCID: PMC3552656  PMID: 22661534
PET/MRI; multimodal imaging; tumor heterogeneity; quantitative molecular imaging; preclinical
3.  Diffusion coefficient measurement using a temperature controlled fluid for quality control in multi-center studies 
To present the use of a quality control ice-water phantom for DW-MRI. DW-MRI has emerged as an important cancer imaging biomarker candidate for diagnosis and early treatment response assessment. Validating imaging biomarkers through multi-center trials requires calibration and performance testing across sites.
Materials and Methods
The phantom consisted of a center tube filled with distilled water surrounded by ice-water. Following preparation of the phantom approximately 30 minutes was allowed to reach thermal equilibrium. DW-MRI data was collected at 7 institutions, 20 MRI scanners from three vendors and 2 field strengths (1.5 and 3T). The phantom was also scanned on a single system on 16 different days over a 25 day period. All data was transferred to a central processing site at the University of Michigan for analysis.
Results revealed that the variation of measured ADC values between all systems tested was ±5% indicating excellent agreement between systems. Reproducibility of a single system over a 25 day period was also found to be within ±5% ADC values. Overall, the use of an ice water phantom for assessment of ADC was found to be a reasonable candidate for use in multi-center trials.
The ice water phantom described here is a practical and universal approach to validate the accuracy of ADC measurements with ever changing MRI sequence and hardware design and can be readily implemented in multicenter clinical trial designs.
PMCID: PMC3177164  PMID: 21928310
diffusion; MRI; phantom; ice water; quality control
4.  dAcquisition setting optimization and quantitative imaging for 124I studies with the Inveon microPET-CT system 
EJNMMI Research  2012;2:7.
Noninvasive multimodality imaging is essential for preclinical evaluation of the biodistribution and pharmacokinetics of radionuclide therapy and for monitoring tumor response. Imaging with nonstandard positron-emission tomography [PET] isotopes such as 124I is promising in that context but requires accurate activity quantification. The decay scheme of 124I implies an optimization of both acquisition settings and correction processing. The PET scanner investigated in this study was the Inveon PET/CT system dedicated to small animal imaging.
The noise equivalent count rate [NECR], the scatter fraction [SF], and the gamma-prompt fraction [GF] were used to determine the best acquisition parameters for mouse- and rat-sized phantoms filled with 124I. An image-quality phantom as specified by the National Electrical Manufacturers Association NU 4-2008 protocol was acquired and reconstructed with two-dimensional filtered back projection, 2D ordered-subset expectation maximization [2DOSEM], and 3DOSEM with maximum a posteriori [3DOSEM/MAP] algorithms, with and without attenuation correction, scatter correction, and gamma-prompt correction (weighted uniform distribution subtraction).
Optimal energy windows were established for the rat phantom (390 to 550 keV) and the mouse phantom (400 to 590 keV) by combining the NECR, SF, and GF results. The coincidence time window had no significant impact regarding the NECR curve variation. Activity concentration of 124I measured in the uniform region of an image-quality phantom was underestimated by 9.9% for the 3DOSEM/MAP algorithm with attenuation and scatter corrections, and by 23% with the gamma-prompt correction. Attenuation, scatter, and gamma-prompt corrections decreased the residual signal in the cold insert.
The optimal energy windows were chosen with the NECR, SF, and GF evaluation. Nevertheless, an image quality and an activity quantification assessment were required to establish the most suitable reconstruction algorithm and corrections for 124I small animal imaging.
PMCID: PMC3311594  PMID: 22330760
small animal imaging; PET/CT; iodine-124; quantitative imaging
5.  A Cone-Shaped Phantom for Assessment of Small Animal PET Scatter Fraction and Count Rate Performance 
Molecular Imaging and Biology  2012;14(5):561-571.
Positron emission tomography (PET) image quality deteriorates as the object size increases owing to increased detection of scattered and random events. The characterization of the scatter component in small animal PET imaging has received little attention owing to the small scatter fraction (SF) when imaging rodents. The purpose of this study is first to design and fabricate a cone-shaped phantom which can be used for measurement of object size-dependent SF and noise equivalent count rates (NECR), and second, to assess these parameters for two small animal PET scanners as function of radial offset, object size and lower energy threshold (LET).
The X-PET™ and LabPET-8™ scanners were modeled as realistically as possible using GATE Monte Carlo simulation platform. The simulation models were validated against experimental measurements in terms of sensitivity, SF and NECR. The dedicated phantom was fabricated in-house using high-density polyethylene. The optimized dimensions of the cone-shaped phantom are 158 mm (length), 20 mm (minimum diameter), 70 mm (maximum diameter) and taper angle of 9°.
The relative difference between simulated and experimental results for the LabPET-8™ scanner varied between 0.7% and 10% except for a few results where it was below 16%. Depending on the radial offset from the center of the central axial field-of-view (3–6 cm diameter), the SF for the cone-shaped phantom varied from 26.3% to 18.2%, 18.6 to 13.1% and 10.1 to 7.6% for the X-PET™, whereas it varied from 34.4% to 26.9%, 19.1 to 17.0% and 9.1 to 7.3% for the LabPET-8™, for LETs of 250, 350 and 425 keV, respectively. The SF increases as the radial offset decreases, LET decreases and object size increases. The SF is higher for the LabPET-8™ compared with the X-PET™ scanner. The NECR increases as the radial offset increases and object size decreases. The maximum NECR was obtained at a LET of 350 keV for the LabPET-8™ and 250 keV for the X-PET™. High correlation coefficients for SF and NECR were observed between the cone-shaped phantom and an equivalent volume cylindrical phantom for the three considered axial fields of view.
A single cone-shaped phantom enables the assessment of the impact of three factors, namely radial offset, LET and object size on PET SF and count rate estimates. This phantom is more realistic owing to the non-uniform shape of rodents’ bodies compared to cylindrical uniform phantoms and seems to be well suited for evaluation of object size-dependent SF and NECR.
PMCID: PMC3443338  PMID: 22311541
PET; Small animals; Scatter; Count rate; Monte Carlo simulation
6.  Visibility of microcalcification in cone beam breast CT − Effects of x-ray tube voltage and radiation dose 
Medical physics  2007;34(7):2995-3004.
Mammography is the only technique currently used for detecting microcalcification (MC) clusters, an early indicator of breast cancer. However, mammographic images superimpose a three-dimensional compressed breast image onto two-dimensional projection views, resulting in overlapped anatomical breast structures that may obscure the detection and visualization of MCs. One possible solution to this problem is the use of cone beam computed tomography (CBCT) with a flat-panel (FP) digital detector. Although feasibility studies of CBCT techniques for breast imaging have yielded promising results, they have not shown how radiation dose and x-ray tube voltage affect the accuracy with which MCs are detected by CBCT experimentally. We therefore conducted a phantom study using FP-based CBCT system with various mean glandular doses and kVp values. An experimental CBCT scanner was constructed with a data-acquisition rate of 7.5 frames/s. 10.5- and 14.5cm-diameter breast phantoms made of gelatin were used to simulate uncompressed breasts consisting of 100% glandular tissue. Eight different MC sizes of calcium carbonate grains, ranging from 180–200 µm to 355–425 µm, were used to simulate MCs. MCs of the same size were arranged to form a 5×5 MC cluster and embedded in the breast phantoms. These MC clusters were positioned at 2.8 cm away from the center of the breast phantoms. The phantoms were imaged at 60, 80, and 100 kVp. With a single scan (360 degrees), 300 projection images were acquired with 0.5×, 1×, and 2× mean glandular dose limit for 10.5-cm phantom and with 1×, 2×, and 4× for 14.5-cm phantom. Feldkamp algorithm with a pure ramp filter was used for image reconstruction. The normalized noise level was calculated for each x-ray tube voltage and dose level. The image quality of CBCT images was evaluated by counting the number of visible MCs for each MC cluster for various conditions. The average percentage of the visible MCs were computed and plotted as a function of the MGD, the kVp, and the average MC size. The results show that the MC visibility increased with the MGD significantly but decreased with the breast size. The results also show the x-ray tube voltage affects the detection of MCs under different circumstances. With a 50% threshold, the minimum detectable MC sizes for the 10.5-cm phantom were 348 (±2), 288 (±7), 257 (±2) µm at 3, 6, and 12 mGy respectively. Those for the 14.5-cm phantom were 355 (±1), 307 (±7), 275 (±5) µm at 6, 12, and 24 mGy, respectively. With a 75% threshold, the minimum detectable MC sizes for the 10.5-cm phantom were 367 (±1), 316 (±7), 265 (±3) µm at 3, 6, and 12 mGy, respectively. Those for the 14.5-cm phantom were 377 (±3), 334 (±5), 300 (±2) µm at 6, 12, and 24 mGy, respectively.
PMCID: PMC2867610  PMID: 17822008
cone-beam computed tomography; breast imaging; flat-panel detector; microcalcifications; mean glandular dose
7.  Development of a Patient-Specific Two-Compartment Anthropomorphic Breast Phantom 
Physics in Medicine and Biology  2012;57(13):4293-4307.
To develop a technique for the construction of a two-compartment anthropomorphic breast phantom specific to an individual patient’s pendant breast anatomy.
Three-dimensional breast images were acquired on a prototype dedicated breast computed tomography (bCT) scanner as part of an ongoing IRB-approved clinical trial of bCT. The images from the breast of a patient were segmented into adipose and glandular tissue regions and divided into 1.59 mm thick breast sections to correspond to the thickness of polyethylene stock. A computer controlled water-jet cutting machine was used to cut the outer breast edge and the internal regions corresponding to glandular tissue from the polyethylene. The stack of polyethylene breast segments was encased in a thermoplastic “skin” and filled with water. Water-filled spaces modeled glandular tissue structures and the surrounding polyethylene modeled the adipose tissue compartment. Utility of the phantom was demonstrated by inserting 200 μm microcalcifications as well as measuring point dose deposition during bCT scanning.
Rigid registration of the original patient images with bCT images of the phantom showed similar tissue distribution. Linear profiles through the registered images demonstrated a mean coefficient of determination (r2) between grayscale profiles of 0.881. The exponent of the power law describing the anatomical noise power spectrum was identical in the coronal images of the patient’s breast and the phantom. Microcalcifications were visualized in the phantom at bCT scanning. Real-time air kerma rate was measured during bCT scanning and fluctuated with breast anatomy. On average, point dose deposition was 7.1% greater than mean glandular dose.
A technique to generate a two-compartment anthropomorphic breast phantom from bCT images has been demonstrated. The phantom is the first, to our knowledge, to accurately model the uncompressed pendant breast and the glandular tissue distribution for a specific patient. The modular design of the phantom allows for studies of a single breast segment and the entire breast volume. Insertion of other devices, materials, and tissues of interest into the phantom provide a robust platform for future breast imaging and dosimetry studies.
PMCID: PMC3404613  PMID: 22705748
Computed tomography; breast; phantom
8.  In vivo Tumor Grading of Prostate Cancer using Quantitative 111In-Capromab Pendetide SPECT/CT 
We have developed an in vivo antibody uptake quantification method using 111In-capromab pendetide single photon emission computed tomography combined with computed tomography (SPECT/CT) technology. Our goal is to evaluate this noninvasive antibody quantification method for potential prostate tumor grading.
Our phantom experiments focused on the robustness of an advanced iterative reconstruction algorithm that involves corrections for photon attenuation, scatter, and geometric blurring caused by radionuclide collimators. The conversion factors between image values and tracer concentrations (in Bq/ml) were calculated from uniform phantom filled with aqueous solution of 111InCl3 using the same acquisition protocol and reconstruction parameters as for patient studies. In addition, the spatial resolution of the reconstructed images was measured from a point source phantom. The measured spatial resolution was modeled into a point spread function (PSF), and the PSF was implemented in a deconvolution-based partial volume error (PVE) correction algorithm. The recovery capability to correctly estimate true tracer concentration values was tested using prostate-like and bladder-like lesion phantoms fitted in the modified NEMA/IEC body phantom. Patients with biopsy-proven prostate cancer (n=10) who underwent prostatectomy were prospectively enrolled in the preoperative SPECT/CT studies at the San Francisco VA Medical Center. The CT portion of SPECT/CT was used for CT-based attenuation map generation as well as an anatomical localization tool for clinical interpretation. Pathologic Gleason grades were compared with in vivo “antibody uptake value” (AUV) normalized by injected dose, effective half-life, and injection-scan time difference. AUVs were calculated in each lobe of prostate gland with cylindrical volumes of interest (VOIs) having dimensions of 1.5 cm both in diameter and height.
Reconstructed SPECT images further corrected by the deconvolution-based PVE correction could recover true tracer concentrations in volumes as small as 7.77 ml up to 90% in phantom measurements. From patient studies, there was a statistically significant correlation (ρ = 0.71, P = 0.033) between higher AUVs (from either left or right lobe) and higher components of pathologic Gleason scores.
Our results strongly indicate noninvasive prostate tumor grading potential using quantitative 111In-capromab pendetide SPECT/CT for prostate cancer evaluation.
PMCID: PMC2821016  PMID: 20008977
prostate cancer; capromab pendetide; SPECT; SPECT/CT; quantification; tracer quantification; quantitative SPECT; prostate specific membrane antigen (PSMA)
9.  Towards a Teleoperated Needle Driver Robot with Haptic Feedback for RFA of Breast Tumors under Continuous MRI1 
Medical image analysis  2009;13(3):445-455.
The purpose of this paper is to explore the feasibility of developing a MRI-compatible needle driver system for radiofrequency ablation (RFA) of breast tumors under continuous MRI imaging while being teleoperated by a haptic feedback device from outside the scanning room. The developed needle driver prototype was designed and tested for both tumor targeting capability as well as RFA.
The single degree-of-freedom (DOF) prototype was interfaced with a PHANToM haptic device controlled from outside the scanning room. Experiments were performed to demonstrate MRI-compatibility and position control accuracy with hydraulic actuation, along with an experiment to determine the PHANToM’s ability to guide the RFA tool to a tumor nodule within a phantom breast tissue model while continuously imaging within the MRI and receiving force feedback from the RFA tool.
Hydraulic actuation is shown to be a feasible actuation technique for operation in an MRI environment. The design is MRI-compatible in all aspects except for force sensing in the directions perpendicular to the direction of motion. Experiments confirm that the user is able to detect healthy vs. cancerous tissue in a phantom model when provided with both visual (imaging) feedback and haptic feedback.
The teleoperated 1-DOF needle driver system presented in this paper demonstrates the feasibility of implementing a MRI-compatible robot for RFA of breast tumors with haptic feedback capability.
PMCID: PMC2698937  PMID: 19303805
Medical robotics; Needle insertion; Radiofrequency ablation (RFA); Haptic feedback; Continuous MRI imaging; Teleoperation
10.  Attenuation Correction for Flexible Magnetic Resonance Coils in Combined Magnetic Resonance/Positron Emission Tomography Imaging 
Investigative radiology  2014;49(2):63-69.
Attenuation correction for magnetic resonance (MR) coils is a new challenge that came about with the development of combined MR and positron emission tomography (PET) imaging. This task is difficult because such coils are not directly visible on either PET or MR acquisitions with current combined scanners and are therefore not easily localized in the field of view. This issue becomes more evident when trying to localize flexible MR coils (eg, cardiac or body matrix coil) that change position and shape from patient to patient and from one imaging session to another. In this study, we proposed a novel method to localize and correct for the attenuation and scatter of a flexible MR cardiac coil, using MR fiducial markers placed on the surface of the coil to allow for accurate registration of a template computed tomography (CT)–based attenuation map.
Materials and Methods
To quantify the attenuation properties of the cardiac coil, a uniform cylindrical water phantom injected with 18F-fluorodeoxyglucose (18F-FDG) was imaged on a sequential MR/PET system with and without the flexible cardiac coil. After establishing the need to correct for the attenuation of the coil, we tested the feasibility of several methods to register a precomputed attenuation map to correct for the attenuation. To accomplish this, MR and CT visible markers were placed on the surface of the cardiac flexible coil. Using only the markers as a driver for registration, the CT image was registered to the reference image through a combination of rigid and deformable registration. The accuracy of several methods was compared for the deformable registration, including B-spline, thin-plate spline, elastic body spline, and volume spline. Finally, we validated our novel approach both in phantom and patient studies.
The findings from the phantom experiments indicated that the presence of the coil resulted in a 10% reduction in measured 18F-FDG activity when compared with the phantom-only scan. Local underestimation reached 22% in regions of interest close to the coil. Various registration methods were tested, and the volume spline was deemed to be the most accurate, as measured by the Dice similarity metric. The results of our phantom experiments showed that the bias in the 18F-FDG quantification introduced by the presence of the coil could be reduced by using our registration method. An overestimation of only 1.9% of the overall activity for the phantom scan with the coil attenuation map was measured when compared with the baseline phantom scan without coil. A local overestimation of less than 3% was observed in the ROI analysis when using the proposed method to correct for the attenuation of the flexible cardiac coil. Quantitative results from the patient study agreed well with the phantom findings.
We presented and validated an accurate method to localize and register a CT-based attenuation map to correct for the attenuation and scatter of flexible MR coils. This method may be translated to clinical use to produce quantitatively accurate measurements with the use of flexible MR coils during MR/PET imaging.
PMCID: PMC4011564  PMID: 24056110
magnetic resonance imaging; positron emission tomography; attenuation correction; flexible radio frequency coils
11.  From RECIST to PERCIST: Evolving Considerations for PET Response Criteria in Solid Tumors 
The purpose of this article is to review the status and limitations of anatomic tumor response metrics including the World Health Organization (WHO) criteria, the Response Evaluation Criteria in Solid Tumors (RECIST), and RECIST 1.1. This article also reviews qualitative and quantitative approaches to metabolic tumor response assessment with 18F-FDG PET and proposes a draft framework for PET Response Criteria in Solid Tumors (PERCIST), version 1.0.
PubMed searches, including searches for the terms RECIST, positron, WHO, FDG, cancer (including specific types), treatment response, region of interest, and derivative references, were performed. Abstracts and articles judged most relevant to the goals of this report were reviewed with emphasis on limitations and strengths of the anatomic and PET approaches to treatment response assessment. On the basis of these data and the authors' experience, draft criteria were formulated for PET tumor response to treatment.
Approximately 3,000 potentially relevant references were screened. Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria is widely applied but still has limitations in response assessments. For example, despite effective treatment, changes in tumor size can be minimal in tumors such as lymphomas, sarcoma, hepatomas, mesothelioma, and gastrointestinal stromal tumor. CT tumor density, contrast enhancement, or MRI characteristics appear more informative than size but are not yet routinely applied. RECIST criteria may show progression of tumor more slowly than WHO criteria. RECIST 1.1 criteria (assessing a maximum of 5 tumor foci, vs. 10 in RECIST) result in a higher complete response rate than the original RECIST criteria, at least in lymph nodes. Variability appears greater in assessing progression than in assessing response. Qualitative and quantitative approaches to 18F-FDG PET response assessment have been applied and require a consistent PET methodology to allow quantitative assessments. Statistically significant changes in tumor standardized uptake value (SUV) occur in careful test–retest studies of high-SUV tumors, with a change of 20% in SUV of a region 1 cm or larger in diameter; however, medically relevant beneficial changes are often associated with a 30% or greater decline. The more extensive the therapy, the greater the decline in SUV with most effective treatments. Important components of the proposed PERCIST criteria include assessing normal reference tissue values in a 3-cm-diameter region of interest in the liver, using a consistent PET protocol, using a fixed small region of interest about 1 cm3 in volume (1.2-cm diameter) in the most active region of metabolically active tumors to minimize statistical variability, assessing tumor size, treating SUV lean measurements in the 1 (up to 5 optional) most metabolically active tumor focus as a continuous variable, requiring a 30% decline in SUV for “response,” and deferring to RECIST 1.1 in cases that do not have 18F-FDG avidity or are technically unsuitable. Criteria to define progression of tumor-absent new lesions are uncertain but are proposed.
Anatomic imaging alone using standard WHO, RECIST, and RECIST 1.1 criteria have limitations, particularly in assessing the activity of newer cancer therapies that stabilize disease, whereas 18F-FDG PET appears particularly valuable in such cases. The proposed PERCIST 1.0 criteria should serve as a starting point for use in clinical trials and in structured quantitative clinical reporting. Undoubtedly, subsequent revisions and enhancements will be required as validation studies are undertaken in varying diseases and treatments.
PMCID: PMC2755245  PMID: 19403881
molecular imaging; oncology; PET/CT; anatomic imaging; RECIST; response criteria; SUV; treatment monitoring
12.  In-phantom dose verification of prostate IMRT and VMAT deliveries using plastic scintillation detectors 
Radiation measurements  2012;47(10):921-929.
The goal of this work was to demonstrate the feasibility of using a plastic scintillation detector (PSD) incorporated into a prostate immobilization device to verify doses in vivo delivered during intensity-modulated radiation therapy (IMRT) and volumetric modulated-arc therapy (VMAT) for prostate cancer. The treatment plans for both modalities had been developed for a patient undergoing prostate radiation therapy. First, a study was performed to test the dependence, if any, of PSD accuracy on the number and type of calibration conditions. This study included PSD measurements of each treatment plan being delivered under quality assurance (QA) conditions using a rigid QA phantom. PSD results obtained under these conditions were compared to ionization chamber measurements. After an optimal set of calibration factors had been found, the PSD was combined with a commercial endorectal balloon used for rectal distension and prostate immobilization during external beam radiotherapy. This PSD-enhanced endorectal balloon was placed inside of a deformable anthropomorphic phantom designed to simulate male pelvic anatomy. PSD results obtained under these so-called “simulated treatment conditions” were compared to doses calculated by the treatment planning system (TPS). With the PSD still inserted in the pelvic phantom, each plan was delivered once again after applying a shift of 1 cm anterior to the original isocenter to simulate a treatment setup error.
The mean total accumulated dose measured using the PSD differed the TPS-calculated doses by less than 1% for both treatment modalities simulated treatment conditions using the pelvic phantom. When the isocenter was shifted, the PSD results differed from the TPS calculations of mean dose by 1.2% (for IMRT) and 10.1% (for VMAT); in both cases, the doses were within the dose range calculated over the detector volume for these regions of steep dose gradient. Our results suggest that the system could benefit prostate cancer patient treatment by providing accurate in vivo dose reports during treatment and verify in real-time whether treatments are being delivered according to the prescribed plan.
PMCID: PMC3501761  PMID: 23180976
in vivo dosimetry; real-time monitoring; plastic scintillation dosimetry
13.  Establishment and Results of a Magnetic Resonance Quality Assurance Program for the Pediatric Brain Tumor Consortium 
Academic radiology  2008;15(9):1099-1110.
Rationale and Objectives: Magnetic resonance (MR) imaging is used to assess brain tumor response to therapies and a MR quality assurance program is necessary for multicenter clinical trials employing imaging. This study was performed to determine overall variability of quantitative image metrics measured with the American College of Radiology (ACR) phantom among 11 sites participating in the Pediatric Brain Tumor Consortium (PBTC) Neuroimaging Center (NIC) MR quality assurance (MR QA) program.
Materials and Methods
An MR QA program was implemented among 11 participating PBTC sites and quarterly evaluations of scanner performance for seven imaging metrics defined by the ACR were sought and subject to statistical evaluation over a 4.5 year period. Overall compliance with the QA program, means, standard deviations and coefficients of variation (CV) for the quantitative imaging metrics were evaluated.
Quantitative measures of the seven imaging metrics were generally within ACR recommended guidelines for all sites. Compliance improved as the study progressed. Inter-site variabilities as gauged by coefficients of variation (CV) for slice thickness and geometric accuracy, imaging parameters that influence size and/or positioning measurements in tumor studies, were on the order of 10 % and 1% respectively.
Although challenging to establish, MR QA programs within the context of PBTC multi-site clinical trials when based on the ACR MR phantom program can a) indicate sites performing below acceptable image quality levels and b) establish levels of precision through instrumental variabilities that are relevant to quantitative image analyses, e.g. tumor volume changes.
PMCID: PMC2561197  PMID: 18692750
Magnetic resonance; quality assurance; pediatric brain tumor; American College of Radiology
14.  Design, manufacture, and analysis of customized phantoms for enhanced quality control in small animal MRI systems 
Magnetic resonance imaging (MRI) is widely used in human brain research to evaluate the effects of healthy aging and development, as well as neurological disorders. Although standardized methods for quality assurance of human MRI instruments have been established, such approaches have typically not been translated to small animal imaging. We present a method for the generation and analysis of customized phantoms for small animal MRI systems that allows rapid and accurate system stability monitoring.
Computer-aided design software was used to produce a customized phantom using a rapid prototyping printer. Automated registration algorithms were used on three dimensional images of the phantom to allow system stability to be easily monitored over time.
The design of the custom phantom allowed reliable placement relative to the imaging g coil. Automated registration showed superior ability to detect gradient changes reflected in the images than with manual measurements. Registering images acquired over time allowed monitoring of gradient drifts of less than one percent.
A low cost, MRI compatible phantom was successfully designed using computer-aided design software and a 3D printer. Registering phantom images acquired over time allows monitoring of gradient stability of the MRI system.
PMCID: PMC3742585  PMID: 23440883
MRI; phantom; quality control
15.  Virtual-Pinhole PET 
We proposed and tested a novel geometry for PET system design analogous to pinhole SPECT called the virtual-pinhole PET (VP-PET) geometry to determine whether it could provide high-resolution images.
We analyzed the effects of photon acolinearity and detector sizes on system resolution and extended the empiric formula for reconstructed image resolution of conventional PET proposed earlier to predict the resolutions of VP-PET. To measure the system resolution of VP-PET, we recorded coincidence events as a 22Na point source was stepped across the coincidence line of response between 2 detectors made from identical arrays of 12 × 12 lutetium oxyorthosilicate crystals (each measuring 1.51 × 1.51 × 10 mm3) separated by 565 mm. To measure reconstructed image resolution, we built 4 VP-PET systems using 4 types of detectors (width, 1.51–6.4mm) and imaged 4 point sources of 64Cu (half-life = 12.7 h to allow a long acquisition time). Tangential and radial resolutions were measured and averaged for each source and each system. We then imaged a polystyrene plastic phantom representing a 2.5-cm-thick cross-section of isolated breast volume. The phantom was filled with an aqueous solution of 64Cu (713 kBq/mL) in which the following were imbedded: 4 spheric tumors ranging from 1.8 to 12.6 mm in inner diameter (ID), 6 micropipettes (0.7- or 1.1-mm ID filled with 64Cu at 5×, 20×, or 50× background), and a 10.0-mm outer-diameter cold lesion.
The shape and measured full width at half maximum of the line spread functions agree well with the predicted values. Measured reconstructed image resolution (2.40–3.24 mm) was ±6% of the predicted value for 3 of the 4 systems. In one case, the difference was 12.6%, possibly due to underestimation of the block effect from the low-resolution detector. In phantom experiments, all spheric tumors were detected. Small line sources were detected if the activity concentration is at least 20× background.
We have developed and characterized a novel geometry for PET. A PET system following the VP-PET geometry provides high-resolution images for objects near the system’s high-resolution detectors. This geometry may lead to the development of special- purpose PET systems or resolution-enhancing insert devices for conventional PET scanners.
PMCID: PMC3024474  PMID: 18287272
PET; geometry; pinhole; breast imaging
16.  Anechoic Sphere Phantoms for Estimating 3-D Resolution of Very High Frequency Ultrasound Scanners 
Two phantoms have been constructed for assessing the performance of high frequency ultrasound imagers. They also allow for periodic quality assurance tests. The phantoms contain eight blocks of tissue-mimicking material where each block contains a spatially random distribution of suitably small anechoic spheres having a small distribution of diameters. The eight mean sphere diameters are distributed from 0.10 to 1.09 mm. The two phantoms differ primarily in terms of the backscatter coefficient of the background material in which the spheres are suspended. The mean scatterer diameter for one phantom is larger than that for the other phantom resulting in a lesser increase in backscatter coefficient for the second phantom; however, the backscatter curves cross at about 35 MHz. Since spheres have no preferred orientation, all three (spatial) dimensions of resolution contribute to sphere detection on an equal basis; thus, the resolution is termed 3-D. Two high frequency scanners are compared. One employs single-element (fixed focus) transducers, and the other employs variable focus linear arrays. The nominal frequency for the single element transducers were 25 and 55 MHz and for the linear array transducers were 20, 30 and 40 MHz. The depth range for detection of spheres of each size is determined corresponding to determination of 3-D resolution as a function of depth. As expected, the single-element transducers are severely limited in useful imaging depth ranges compared with the linear arrays. Note that these phantoms could also be useful for training technicians in using higher frequency scanners.
PMCID: PMC3769966  PMID: 20889416
3-D resolution; high frequency; phantoms; ultrasound
17.  Contrast-enhanced small-animal PET/CT in cancer research: strong improvement of diagnostic accuracy without significant alteration of quantitative accuracy and NEMA NU 4–2008 image quality parameters 
EJNMMI Research  2013;3:5.
The use of iodinated contrast media in small-animal positron emission tomography (PET)/computed tomography (CT) could improve anatomic referencing and tumor delineation but may introduce inaccuracies in the attenuation correction of the PET images. This study evaluated the diagnostic performance and accuracy of quantitative values in contrast-enhanced small-animal PET/CT (CEPET/CT) as compared to unenhanced small animal PET/CT (UEPET/CT).
Firstly, a NEMA NU 4–2008 phantom (filled with 18F-FDG or 18F-FDG plus contrast media) and a homemade phantom, mimicking an abdominal tumor surrounded by water or contrast media, were used to evaluate the impact of iodinated contrast media on the image quality parameters and accuracy of quantitative values for a pertinent-sized target. Secondly, two studies in 22 abdominal tumor-bearing mice and rats were performed. The first animal experiment studied the impact of a dual-contrast media protocol, comprising the intravenous injection of a long-lasting contrast agent mixed with 18F-FDG and the intraperitoneal injection of contrast media, on tumor delineation and the accuracy of quantitative values. The second animal experiment compared the diagnostic performance and quantitative values of CEPET/CT versus UEPET/CT by sacrificing the animals after the tracer uptake period and imaging them before and after intraperitoneal injection of contrast media.
There was minimal impact on IQ parameters (%SDunif and spillover ratios in air and water) when the NEMA NU 4–2008 phantom was filled with 18F-FDG plus contrast media. In the homemade phantom, measured activity was similar to true activity (−0.02%) and overestimated by 10.30% when vials were surrounded by water or by an iodine solution, respectively. The first animal experiment showed excellent tumor delineation and a good correlation between small-animal (SA)-PET and ex vivo quantification (r2 = 0.87, P < 0.0001). The second animal experiment showed a good correlation between CEPET/CT and UEPET/CT quantitative values (r2 = 0.99, P < 0.0001). Receiver operating characteristic analysis demonstrated better diagnostic accuracy of CEPET/CT versus UEPET/CT (senior researcher, area under the curve (AUC) 0.96 versus 0.77, P = 0.004; junior researcher, AUC 0.78 versus 0.58, P = 0.004).
The use of iodinated contrast media for small-animal PET imaging significantly improves tumor delineation and diagnostic performance, without significant alteration of SA-PET quantitative accuracy and NEMA NU 4–2008 IQ parameters.
PMCID: PMC3563455  PMID: 23327687
Small-animal PET/CT; Contrast media; NEMA NU 4–2008; Tumor-bearing rodents; Quantification
18.  Detection of simulated microcalcifications in a phantom with digital mammography: effect of pixel size 
Radiology  2007;244(1):130-137.
To evaluate the effect of pixel size on the detection of simulated microcalcifications in digital mammography using a phantom.
A high-resolution prototype imager with variable pixel size of 39 and 78 μm, and a clinical full-field digital mammography (FFDM) system with pixel size of 100 μm were used. X-ray images of a contrast-detail (CD) phantom were obtained to perform alternative forced choice (AFC) observer experiments. Polymethyl-methacrylate (PMMA) was added to obtain phantom thickness of 45 and 58 mm which are typical breast thickness conditions encountered in mammography. Phantom images were acquired with both systems under nearly identical exposure conditions using an anti-scatter grid. Twelve images were acquired for each phantom thickness and pixel size (total of 72 images) and six observers participated in this study. Observer responses were used to compute the fraction of correctly detected disks. A signal detection model was used to fit the recorded data from which CD characteristics were obtained. Repeated-measures analyses using mixed effects linear models were performed for each of the 6 observers. All statistical tests were 2-sided and unadjusted for multiple comparisons. A P value of 0.05 or less was considered to indicate statistical significance.
Statistical analysis indicated significantly better CD characteristics with 39 and 78 μm pixel sizes compared to the 100 μm pixel for all disk diameters and phantom thickness conditions (p<0.001). Increase in phantom thickness degraded CD characteristics irrespective of pixel size (p<0.001).
Based on the conditions of this study, reducing pixel size below 100 μm with low imaging system noise enhances the visual perception of small objects that correspond to typical microcalcification size.
PMCID: PMC2430729  PMID: 17522348
19.  Simultaneous Acquisition of Magnetic Resonance Spectroscopy (MRS) Data and Positron Emission Tomography (PET) Images with a Prototype MR Compatible, Small Animal PET Imager 
Multimodality imaging (such as PET-CT) is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET, fused with anatomical images created by MRI, allow the correlation of form with function. Perhaps more exciting than the combination of anatomical MRI with PET, is the melding of PET with MR Spectroscopy (MRS). Thus, two aspects of physiology could be combined in novel ways to produce new insights into the physiology of normal and pathological processes. Our team is developing a system to acquire MRI images and MRS spectra, and PET images contemporaneously. The prototype MR-compatible PET system consists of two opposed detector heads (appropriate in size for small animal imaging), operating in coincidence mode with an active field-of-view of ~14cm in diameter. Each detector consists of an array of LSO detector elements coupled through a 2m long fiber optic light guide to a single position-sensitive photomultiplier tube. The use of light guides allows these magnetic field-sensitive elements of the PET imager to be positioned outside the strong magnetic field of our 3T MRI scanner. The PET scanner imager was integrated with a 12cm diameter, 12-leg custom, birdcage coil. Simultaneous MRS spectra and PET images were successfully acquired from a multi-modality phantom consisting of a sphere filled with seventeen brain relevant substances and a positron-emitting radionuclide. There were no significant changes in MRI or PET scanner performance when both were present in the MRI magnet bore. This successful initial test demonstrates the potential for using such a multi-modality to obtain complementary MRS and PET data.
PMCID: PMC1950253  PMID: 17433742
Positron Emission Tomography; Magnetic Resonance Spectroscopy
20.  Limitations of Airway Dimension Measurement on Images Obtained Using Multi-Detector Row Computed Tomography 
PLoS ONE  2013;8(10):e76381.
(a) To assess the effects of computed tomography (CT) scanners, scanning conditions, airway size, and phantom composition on airway dimension measurement and (b) to investigate the limitations of accurate quantitative assessment of small airways using CT images.
An airway phantom, which was constructed using various types of material and with various tube sizes, was scanned using four CT scanner types under different conditions to calculate airway dimensions, luminal area (Ai), and the wall area percentage (WA%). To investigate the limitations of accurate airway dimension measurement, we then developed a second airway phantom with a thinner tube wall, and compared the clinical CT images of healthy subjects with the phantom images scanned using the same CT scanner. The study using clinical CT images was approved by the local ethics committee, and written informed consent was obtained from all subjects. Data were statistically analyzed using one-way ANOVA.
Errors noted in airway dimension measurement were greater in the tube of small inner radius made of material with a high CT density and on images reconstructed by body algorithm (p<0.001), and there was some variation in error among CT scanners under different fields of view. Airway wall thickness had the maximum effect on the accuracy of measurements with all CT scanners under all scanning conditions, and the magnitude of errors for WA% and Ai varied depending on wall thickness when airways of <1.0-mm wall thickness were measured.
The parameters of airway dimensions measured were affected by airway size, reconstruction algorithm, composition of the airway phantom, and CT scanner types. In dimension measurement of small airways with wall thickness of <1.0 mm, the accuracy of measurement according to quantitative CT parameters can decrease as the walls become thinner.
PMCID: PMC3792973  PMID: 24116105
21.  Performance Evaluation of the Inveon Dedicated PET Preclinical Tomograph Based on the NEMA-NU4 Standards 
The Inveon dedicated PET (DPET) tomograph is the latest generation of preclinical PET systems dedicated to high resolution and high sensitivity murine model imaging. Here, we report on its performance based on the NEMA NU-4 standards.
The Inveon DPET consists of 64 lutetium oxyorthosilicate (LSO) block detectors arranged in 4 contiguous rings, with a 16.1 cm ring diameter and a 12.7 cm axial length. Each detector block consists of a 20×20 LSO crystal array of 1.51×1.51×10.0 mm3 elements. The scintillation light is transmitted to position-sensitive photomultiplier tubes via optical light guides. Energy resolution, spatial resolution, sensitivity, scatter fraction and count rate performance were evaluated. The NEMA NU-4 image quality phantom and a normal mouse injected with 18FDG and 18F− were scanned to evaluate its imaging capability.
The energy resolution at 511 keV was 14.6% on average for the entire system. In-plane radial and tangential resolutions reconstructed with Fourier rebinning and filtered backprojection algorithms were below 1.8 mm full width at half maximum (FWHM) at the center of field of view (FOV). The radial and tangential resolution remained under 2.0 mm and the axial resolution remained under 3.0 mm FWHM within the central 4 cm diameter FOV. The absolute sensitivity of the system was measured to be 9.3% for an energy window of 250–625 keV and a timing window of 3.432 ns. The peak NECR at a 350–625 keV energy window and a 3.432 ns timing window was 1670 kcps at 130 MBq for the mouse-sized phantom and 590 kcps at 110 MBq for the rat-sized phantom. The scatter fractions at the same acquisition settings were 7.8% and 17.2% for the mouse- and rat-sized phantoms, respectively. The mouse image quality phantom results demonstrate that for typical mouse acquisitions, the image quality correlates well to the measured performance parameters in terms of image uniformity, recovery coefficients, attenuation and scatter corrections.
The Inveon system shows significantly improved energy resolution, sensitivity, axial coverage and count rate capabilities compared to previous generations of preclinical PET systems from the same manufacturer. Its performance is suitable for successful murine model imaging experiments.
PMCID: PMC2803022  PMID: 19223424
microPET; small-animal PET scanner; performance evaluation; instrumentation; molecular imaging
22.  Signal Fluctuations Induced by non-T1-related Confounds in Variable TR fMRI Experiments 
To assess and model signal fluctuations induced by non-T1-related confounds in variable repetition time fMRI and to develop a compensation procedure to correct for the non-T1- related artifacts.
Materials and Methods
Radio-frequency disabled volume gradient sequences were effected at variable offsets between actual image acquisitions, enabling perturbation of the measurement system without perturbing longitudinal magnetization, allowing the study of non-T1-related confounds that may arise in variable TR experiments. Three imaging sessions utilizing a daily quality assurance (DQA) phantom were conducted to assess the signal fluctuations, which were then modeled as a second order system. A modified projection procedure was implemented to correct for signal fluctuations arising from non-T1-related confounds, and statistical analysis was performed to assess the significance of the artifacts with and without compensation.
Assessment using phantom data reveals that the signal fluctuations induced by non-T1- related confounds was consistent in shape across the phantom and well-modeled by a second order system. The phantom exhibited significant spurious detections (at p < 0.01) almost uniformly across the central slices of the phantom. Second-order system modeling and compensation of non-T1-related confounds achieves significant reduction of spurious detection of fMRI activity in a phantom.
PMCID: PMC2728024  PMID: 19388103
variable TR; non-T1-related artifacts; eddy currents; gradient coil heating
23.  Automatic polyp detection and measurement with computed tomographic colonography: A phantom study 
The purpose of this study is to assess the performance of computer-aided detection (CAD) software in detecting and measuring polyps for CT Colonography, based on an in vitro phantom study.
Material and methods
A colon phantom was constructed with a PVC pipe of 3.8 cm diameter. Nine simulated polyps of various sizes (3.2mm-25.4mm) were affixed inside the phantom that was placed in a water bath. The phantom was scanned on a 64-slice CT scanner with tube voltage of 120 kV and current of 205 mAs. Two separate scans were performed, with different slice thickness and reconstruction interval. The first scan (thin) had a slice thickness of 1mm and reconstruction interval 0.5mm. The second scan (thick) had a slice thickness of 2mm and reconstruction interval of 1mm. Images from both scans were processed using CT Colonography software that automatically segments the colon phantom and applies CAD that automatically highlights and provides the size (maximum and minimum diameters, volume) of each polyp. Two readers independently measured each polyp (two orthogonal diameters) using both 2D and 3D views. Readers’ manual measurements (diameters) and automatic measurements from CAD (diameters and volume) were compared to actual polyp sizes as measured by mechanical calipers.
All polyps except the smallest (3.2mm) were detected by CAD. CAD achieved 100% sensitivity in detecting polyps ≥6mm. Mean errors in CAD automated volume measurements for thin and thick slice scans were 8.7% and 6.8%, respectively. Almost all CAD and manual readers’ 3D measurements overestimated the size of polyps to variable extent. Both over- and underestimation of polyp sizes were observed in the readers’ manual 2D measurements. Overall, Reader 1 (expert) had smaller mean error than Reader 2 (non-expert).
CAD provided accurate size measurements for all polyps, and results were comparable to the two readers' manual measurements
PMCID: PMC3097787  PMID: 21611052
Polyp measurement; CT colonography; CAD; automatic measurement
24.  The development, validation and application of a multi-detector CT (MDCT) scanner model for assessing organ doses to the pregnant patient and the fetus using Monte Carlo simulations 
Physics in Medicine and Biology  2009;54(9):2699-2717.
The latest multiple-detector technologies have further increased the popularity of x-ray CT as a diagnostic imaging modality. There is a continuing need to assess the potential radiation risk associated with such rapidly evolving multi-detector CT (MDCT) modalities and scanning protocols. This need can be met by the use of CT source models that are integrated with patient computational phantoms for organ dose calculations. Based on this purpose, this work developed and validated an MDCT scanner using the Monte Carlo method, and meanwhile the pregnant patient phantoms were integrated into the MDCT scanner model for assessment of the dose to the fetus as well as doses to the organs or tissues of the pregnant patient phantom. A Monte Carlo code, MCNPX, was used to simulate the x-ray source including the energy spectrum, filter and scan trajectory. Detailed CT scanner components were specified using an iterative trial-and-error procedure for a GE LightSpeed CT scanner. The scanner model was validated by comparing simulated results against measured CTDI values and dose profiles reported in the literature. The source movement along the helical trajectory was simulated using the pitch of 0.9375 and 1.375, respectively. The validated scanner model was then integrated with phantoms of a pregnant patient in three different gestational periods to calculate organ doses. It was found that the dose to the fetus of the 3 month pregnant patient phantom was 0.13 mGy/100 mAs and 0.57 mGy/100 mAs from the chest and kidney scan, respectively. For the chest scan of the 6 month patient phantom and the 9 month patient phantom, the fetal doses were 0.21 mGy/100 mAs and 0.26 mGy/100 mAs, respectively. The paper also discusses how these fetal dose values can be used to evaluate imaging procedures and to assess risk using recommendations of the report from AAPM Task Group 36. This work demonstrates the ability of modeling and validating an MDCT scanner by the Monte Carlo method, as well as assessing fetal and organ doses by combining the MDCT scanner model and the pregnant patient phantom.
PMCID: PMC3376893  PMID: 19351983
25.  Development of a MicroCT-Based Image-Guided Conformal Radiotherapy System for Small Animals 
The need for clinically-relevant radiation therapy technology for the treatment of preclinical models of disease has spurred the development of a variety of dedicated platforms for small animal irradiation. Our group has taken the approach of adding the ability to deliver conformal radiotherapy to an existing 120 kVp micro-computed tomography (microCT) scanner.
A GE eXplore RS120 microCT scanner was modified by the addition of a two-dimensional subject translation stage and a variable aperture collimator. Quality assurance protocols for these devices, including measurement of translation stage positioning accuracy, collimator aperture accuracy, and collimator alignment with the x-ray beam, were devised. Use of this system for image-guided radiotherapy was assessed by irradiation of a solid water phantom as well as of two mice bearing spontaneous MYC-induced lung tumors. Radiation damage was assessed ex vivo by immunohistochemical detection of γH2AX foci.
The positioning error of the translation stage was found to be less than 0.05 mm, while after alignment of the collimator with the x-ray axis through adjustment of its displacement and rotation, the collimator aperture error was less than 0.1 mm measured at isocenter. CT image-guided treatment of a solid water phantom demonstrated target localization accuracy to within 0.1 mm. γH2AX foci were detected within irradiated lung tumors in mice, with contralateral lung tissue displaying background staining.
Addition of radiotherapy functionality to a microCT scanner is an effective means of introducing image-guided radiation treatments into the preclinical setting. This approach has been shown to facilitate small animal conformal radiotherapy while leveraging existing technology.
PMCID: PMC2906632  PMID: 20395069
Mouse models; Radiotherapy; Image guidance; MicroCT

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