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1.  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
2.  Phantom-based quality assurance measurements in B-mode ultrasound 
Acta Radiologica Short Reports  2013;2(8):2047981613511967.
Recommended phantom-based quality assurance measurements in B-mode ultrasound (US) may be tedious. For the purpose of cost-effective US quality assurance it is important to evaluate measurements that effectively reflect the quality of US scanner.
To find out which recommended phantom-based quality assurance measurements are effective in detecting dead or weak transducer elements or channels in US scanners when visual image analysis and manual measurements are used.
Material and Methods
Altogether 66 transducers from 33 US scanners were measured using a general purpose phantom and a transducer tester. The measurements were divided into two groups. Group I consisted of phantom-based uniformity measurement, imaging the air with a clean transducer (air image) and measuring the transducer with the transducer tester, and group II of phantom-based measurements of depth of penetration, beam profile, near field, axial and lateral resolution, and vertical and horizontal distance accuracy. The group II measurements were compared to group I measurements.
With group I measurements, the results with 20% of the transducers were found defective. With 35% of the transducers the results were considered defective in group II measurements. Concurrent flaws in both groups were found with 11% of the transducers.
Phantom-based measurements of depth of penetration, beam profile, near field, axial and lateral resolution, and vertical and horizontal distance accuracy did not consistently detect dead or weak transducer elements or channels in US scanners.
PMCID: PMC3863967  PMID: 24349715
Ultrasound; quality assurance; quality control; acceptance testing
3.  Review of Failed CT Phantom Image Evaluations in 2005 and 2006 by the CT Accreditation Program of the Korean Institute for Accreditation of Medical Image 
Korean Journal of Radiology  2008;9(4):354-363.
The CT accreditation program was established in 2004 by the Korean Institute for Accreditation of Medical Image (KIAMI) to confirm that there was proper quality assurance of computed tomography (CT) images. We reviewed all the failed CT phantom image evaluations performed in 2005 and 2006.
Materials and Methods
We analyzed 604 failed CT phantom image evaluations according to the type of evaluation, the size of the medical institution, the parameters of the phantom image testing and the manufacturing date of the CT scanners.
The failure rates were 10.5% and 21.6% in 2005 and 2006, respectively. Spatial resolution was the most frequently failed parameter for the CT phantom image evaluations in both years (50.5% and 49%, respectively). The proportion of cases with artifacts increased in 2006 (from 4.5% to 37.8%). The failed cases in terms of image uniformity and the CT number of water decreased in 2006. The failure rate in general hospitals was lower than at other sites. In 2006, the proportion of CT scanners manufactured before 1995 decreased (from 12.9% to 9.3%).
The continued progress in the CT accreditation program may achieve improved image quality and thereby improve the national health of Korea.
PMCID: PMC2627278  PMID: 18682674
Computed tomography (CT); Quality assurance; Image quality; Phantoms
4.  Translational imaging endpoints to predict treatment response to novel targeted anticancer agents 
Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) Criteria have been traditionally used for the evaluation of therapeutic response to chemotherapeutic treatment regimens. They determine anatomic criteria for patients response to anti-cancer therapy based on morphological measurements of each target lesion. While this assessment is justified for cytotoxic (chemotherapeutic) drugs, it is now recognized that morphological imaging protocols are poorly suited to the evaluation of the efficacy of novel signal transduction inhibitors (STIs) which exhibit cytostatic rather than cytotoxic properties. New imaging technologies are now designed to evaluate, in a functional manner, modifications in tumor metabolic activity, cellularity, vascularization before a reduction in tumor volume can be detected. Introduction of physiological imaging end-points, derived from dynamic contrast-enhanced (DCE) imaging protocols – including magnetic resonance imaging (MRI), computed tomography (CT) and ultrasound (US) - allow for early assessment of disruption in tumor perfusion and permeability for targeted anti-angiogenic agents. Diffusion-weighted MRI (DWI) provides another physiological imaging end-point since tumor necrosis and cellularity are seen early in response to anti-angiogenic treatment. Changes in glucose and phospholipid turnover, based on metabolic MRI and positron emission tomography (PET), provide reliable markers for therapeutic response to novel receptor-targeting agents. Finally, novel molecular imaging techniques of protein and gene expression have been developed in animal models followed by a successful human application for gene therapy-based protocols.
PMCID: PMC3159818  PMID: 21640633
functional imaging; magnetic resonance imaging; positron emission tomography; signal transduction inhibitors; contrast enhanced imaging; personalized medicine
5.  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
6.  Investigation of the usability of conebeam CT data sets for dose calculation 
To investigate the feasibility and accuracy of dose calculation in cone beam CT (CBCT) data sets.
Kilovoltage CBCT images were acquired with the Elekta XVI system, CT studies generated with a conventional multi-slice CT scanner (Siemens Somatom Sensation Open) served as reference images. Material specific volumes of interest (VOI) were defined for commercial CT Phantoms (CATPhan® and Gammex RMI®) and CT values were evaluated in CT and CBCT images. For CBCT imaging, the influence of image acquisition parameters such as tube voltage, with or without filter (F1 or F0) and collimation on the CT values was investigated. CBCT images of 33 patients (pelvis n = 11, thorax n = 11, head n = 11) were compared with corresponding planning CT studies. Dose distributions for three different treatment plans were calculated in CT and CBCT images and differences were evaluated. Four different correction strategies to match CT values (HU) and density (D) in CBCT images were analysed: standard CT HU-D table without adjustment for CBCT; phantom based HU-D tables; patient group based HU-D tables (pelvis, thorax, head); and patient specific HU-D tables.
CT values in the CBCT images of the CATPhan® were highly variable depending on the image acquisition parameters: a mean difference of 564 HU ± 377 HU was calculated between CT values determined from the planning CT and CBCT images. Hence, two protocols were selected for CBCT imaging in the further part of the study and HU-D tables were always specific for these protocols (pelvis and thorax with M20F1 filter, 120 kV; head S10F0 no filter, 100 kV). For dose calculation in real patient CBCT images, the largest differences between CT and CBCT were observed for the standard CT HU-D table: differences were 8.0% ± 5.7%, 10.9% ± 6.8% and 14.5% ± 10.4% respectively for pelvis, thorax and head patients using clinical treatment plans. The use of patient and group based HU-D tables resulted in small dose differences between planning CT and CBCT: 0.9% ± 0.9%, 1.8% ± 1.6%, 1.5% ± 2.5% for pelvis, thorax and head patients, respectively. The application of the phantom based HU-D table was acceptable for the head patients but larger deviations were determined for the pelvis and thorax patient populations.
The generation of three HU-D tables specific for the anatomical regions pelvis, thorax and head and specific for the corresponding CBCT image acquisition parameters resulted in accurate dose calculation in CBCT images. Once these HU-D tables are created, direct dose calculation on CBCT datasets is possible without the need of a reference CT images for pixel value calibration.
PMCID: PMC2648965  PMID: 19087250
7.  Dual-Energy CT in Patients Treated with Anti-Angiogenic Agents for Non-Small Cell Lung Cancer: New Method of Monitoring Tumor Response? 
Korean Journal of Radiology  2012;13(6):702-710.
To evaluate tumor responses in patients treated with anti-angiogenic agents for non-small cell lung cancer (NSCLC) by assessing intratumoral changes using a dual-energy CT (DECT) (based on Choi's criteria) and to compare it to traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria.
Materials and Methods
Ten NSCLC patients treated with bevacizumab underwent DECT. Tumor responses to anti-angiogenic therapy were assessed and compared with the baseline CT results using both RECIST (size changes only) and Choi's criteria (reflecting net tumor enhancement). Kappa statistics was used to evaluate agreements between tumor responses assessed by RECIST and Choi's criteria.
The weighted κ value for the comparison of tumor responses between the RECIST and Choi's criteria was 0.72. Of 31 target lesions (21 solid nodules, 8 lymph nodes, and two ground-glass opacity nodules [GGNs]), five lesions (16%) showed discordant responses between RECIST and Choi's criteria. Iodine-enhanced images allowed for a distinction between tumor enhancement and hemorrhagic response (detected in 14% [4 of 29, excluding GGNs] of target lesions on virtual nonenhanced images).
DECT may serve as a useful tool for response evaluation after anti-angiogenic treatment in NSCLC patients by providing information on the net enhancement of target lesions without obtaining non-enhanced images.
PMCID: PMC3484290  PMID: 23118568
Targeted therapy; Tumor response assessment; Response criteria; Guideline; Non-small cell lung cancer; Dual energy CT
8.  Modification of the NEMA XR21-2000 cardiac phantom for testing of imaging systems used in endovascular image guided interventions 
X-ray equipment testing using phantoms that mimic the specific human anatomy, morphology, and structure is a very important step in the research, development, and routine quality assurance for such equipment. Although the NEMA XR21 phantom exists for cardiac applications, there is no such standard phantom for neuro-, peripheral and cardio-vascular angiographic applications. We have extended the application of the NEMA XR21-2000 phantom to evaluate neurovascular x-ray imaging systems by structuring it to be head-equivalent; two aluminum plates shaped to fit into the NEMA phantom geometry were added to a 15 cm thick section. Also, to enable digital subtraction angiography (DSA) testing, two replaceable central plates with a hollow slot were made so that various angiographic sections could be inserted into the phantom. We tested the new modified phantom using a flat panel C-arm unit dedicated for endovascular image-guided interventions. All NEMA XR21-2000 standard test sections were used in evaluations with the new “head-equivalent” phantom. DSA and DA are able to be tested using two standard removable blocks having simulated arteries of various thickness and iodine concentrations (AAPM Report 15). The new phantom modifications have the benefits of enabling use of the standard NEMA phantom for angiography in both neuro- and cardio-vascular applications, with the convenience of needing only one versatile phantom for multiple applications. Additional benefits compared to using multiple phantoms are increased portability and lower cost.
PMCID: PMC2743264  PMID: 19756259
Cardiac and Neurovascular phantom; NEMA XR21; digital angiography phantom; digital subtracted angiography phantom
9.  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
10.  Assessing the image quality of pelvic MR images acquired with a flat couch for radiotherapy treatment planning 
The British Journal of Radiology  2011;84(1004):750-755.
To improve the integration of MRI with radiotherapy treatment planning, our department fabricated a flat couch top for our MR scanner. Setting up using this couch top meant that the patients were physically higher up in the scanner and, posteriorly, a gap was introduced between the patient and radiofrequency coil.
Phantom measurements were performed to assess the quantitative impact on image quality. A phantom was set up with and without the flat couch insert in place, and measurements of image uniformity and signal to noise were made. To assess clinical impact, six patients with pelvic cancer were recruited and scanned on both couch types. The image quality of pairs of scans was assessed by two consultant radiologists.
The use of the flat couch insert led to a drop in image signal to noise of approximately 14%. Uniformity in the anteroposterior direction was affected the most, with little change in right-to-left and feet-to-head directions. All six patients were successfully scanned on the flat couch, although one patient had to be positioned with their arms by their sides. The image quality scores showed no statistically significant change between scans with and without the flat couch in place.
Although the quantitative performance of the coil is affected by the integration of a flat couch top, there is no discernible deterioration of diagnostic image quality, as assessed by two consultant radiologists. Although the flat couch insert moved patients higher in the bore of the scanner, all patients in the study were successfully scanned.
PMCID: PMC3473431  PMID: 21750138
11.  Prostate Cancer Clinical Trial End Points: ‘‘RECIST’’ing a Step Backwards 
To relate clinical issues to the clinical manifestations of prostate cancers across disease states using the eligibility and outcome criteria defined by Response Evaluation Criteria in Solid Tumors (RECIST).
Experimental Design
The manifestations of prostate cancer that characterize localized, recurrent, and metastatic disease were considered using the eligibility criteria for trials defined by RECIST. To do so, we analyzed the sites, size, and distribution of lesions in patients enrolled on contemporary Institutional Review Board ^ approved trials for progressive castrate and noncastrate metastatic disease. Prostate-specific antigen (PSA) levels were also assessed. RECIST-defined outcome measures for tumor regression were then applied to the metastatic patient cohorts, and separately to the states of a rising PSA (noncastrate and castrate) and localized disease.
Only 43.5% of men with castrate metastatic and16% of noncastrate metastatic disease had measurable target lesions >2 cmin size. Overall, 84.4% of the target lesions were lymphnodes, of which 67.7% were ≥2 cm in the long axis. There are no target lesions in patients in the states of a rising PSA and localized disease, making them ineligible for trials under these criteria. PSA-based eligibility and outcomes under RECIST conflict with established reporting standards for the states of a rising PSA and castrate metastatic disease. The clinical manifestations of prostate cancer across multiple disease states are not addressed adequately using the eligibility criteria and outcomes measures defined by RECIST. Important treatment effects are not described.
Trial eligibility and end points based solely on tumor regression are not applicable to the majority of the clinical manifestations of prostate cancers representing all clinical states. Treatment effects can be described more precisely if eligibility criteria are adapted to the clinical question being addressed and clinical state under study, focusing on the duration of benefit defined biochemically, radiographically, and/or clinically.
PMCID: PMC1852496  PMID: 16033840
12.  The Role of Magnetic Resonance Imaging Biomarkers in Clinical Trials of Treatment Response in Cancer 
Seminars in oncology  2011;38(1):16-25.
Current standard-of-care radiological methods for assessing the response of solid tumors to treatment are based on measuring changes in lesion size in a single dimension using high-resolution x-ray computed tomography or magnetic resonance imaging (MRI). Even if size measurements are adapted to record true volume changes more accurately, the effects of therapeutic drugs on tumor size may not occur for several cycles of treatment. Furthermore, current and future generations of anti-cancer drugs will be designed to affect highly specific cancer characteristics, and their effects may not be immediately cytotoxic. More sensitive and specific measures are required that can report on tumor status and treatment response early in the course of therapy. Several MRI techniques have matured to the point where they can offer quantitative information on tissue status and greater insight into specific biophysical and physiological characteristics of tumors. Here we review and provide illustrative examples of two MRI methods that have already been incorporated into clinical trials of treatment response in solid tumors: diffusion imaging and dynamic contrast enhanced MRI. We also discuss the limitations and future research directions required for these techniques to gain greater acceptance and to have their maximum impact.
PMCID: PMC3073543  PMID: 21362513
13.  Molecularly Targeted Therapy Using Bevacizumab for Non-Small Cell Lung Cancer: a Pilot Study for the New CT Response Criteria 
Korean Journal of Radiology  2010;11(6):618-626.
We wanted to compare the efficacy of the new CT response evaluation criteria for predicting the tumor progression-free survival (PFS) with that of RECIST 1.1 in non-small cell lung cancer (NSCLC) patients who were treated with bevacizumab.
Materials and Methods
Sixteen patients (M:F = 11:5; median age, 57 years) treated with bevacizumab and combined cytotoxic chemotherapeutic agents were selected for a retrospective analysis. The tumor response was assessed by four different methods, namely, by using RECIST 1.1 (RECIST), RECIST but measuring only the solid component of tumor (RECISTsolid), the alternative method reflecting tumor cavitation (the alternative method) and the combined criteria (the combined criteria) that evaluated both the changes of tumor size and attenuation. To evaluate the capabilities of the different measurement methods to predict the patient prognosis, the PFS were compared, using the log rank test, among the responder groups (complete response [CR], partial response [PR], stable disease [SD] and progressive disease [PD]) in terms of the four different methods.
The overall (CR, PR or SD) response rates according to RECIST, RECISTsolid, the alternative method and the combined criteria were 81%, 88%, 81% and 85%, respectively. The confirmed response rates (CR or PR) were 19%, 19%, 50% and 54%, respectively. Although statistically not significant, the alternative method showed the biggest difference for predicting PFS among the three response groups (PR, SD and PD) (p = 0.07). RECIST and the alternative method showed a significant difference for predicting the prognosis between the good (PR or SD) and poor overall responders (p = 0.02).
The response outcome evaluations using the three different CT response criteria that reflect tumor cavitation, the ground-glass opacity component and the attenuation changes in NSCLC patients treated with bevacizumab showed different results from that with using the traditional RECIST method.
PMCID: PMC2974223  PMID: 21076587
Targeted therapy; Tumor response assessment; Response criteria; Guideline, Non-small cell lung cancer
14.  Evaluation of imaging performance of megavoltage cone-beam CT over an extended period 
Journal of Radiation Research  2013;55(1):191-199.
A linear accelerator vendor and the AAPM TG-142 report propose that quality assurance testing for image-guided devices such megavoltage cone-beam CT (MV-CBCT) be conducted on a monthly basis. In clinical settings, however, unpredictable errors such as image artifacts can occur even when quality assurance results performed at this frequency are within tolerance limits. Here, we evaluated the imaging performance of MV-CBCT on a weekly basis for ∼ 1 year using a Siemens ONCOR machine with a 6-MV X-ray and an image-quality phantom. Image acquisition was undertaken using 15 monitor units. Geometric distortion was evaluated with beads evenly distributed in the phantom, and the results were compared with the expected position in three dimensions. Image-quality characteristics of the system were measured and assessed qualitatively and quantitatively, including image noise and uniformity, low-contrast resolution, high-contrast resolution and spatial resolution. All evaluations were performed 100 times each. For geometric distortion, deviation between the measured and expected values was within the tolerance limit of 2 mm. However, a subtle systematic error was found which meant that the phantom was rotated slightly in a clockwise manner, possibly due to geometry calibration of the MV-CBCT system. Regarding image noise and uniformity, two incidents over tolerance occurred in 100 measurements. This phenomenon disappeared after dose calibration of beam output for MV-CBCT. In contrast, all results for low-contrast resolution, high-contrast resolution and spatial resolution were within their respective tolerances.
PMCID: PMC3885132  PMID: 23979076
Cone-beam CT; QA; image-guided radiation therapy; IGRT; tolerance; calibration
15.  Tissue phantoms in multicenter clinical trials for diffuse optical technologies 
Biomedical Optics Express  2012;3(5):966-971.
Tissue simulating phantoms are an important part of instrumentation validation, standardization/training and clinical translation. Properly used, phantoms form the backbone of sound quality control procedures. We describe the development and testing of a series of optically turbid phantoms used in a multi-center American College of Radiology Imaging Network (ACRIN) clinical trial of Diffuse Optical Spectroscopic Imaging (DOSI). The ACRIN trial is designed to measure the response of breast tumors to neoadjuvant chemotherapy. Phantom measurements are used to determine absolute instrument response functions during each measurement session and assess both long and short-term operator and instrument reliability.
PMCID: PMC3342201  PMID: 22567589
(350.4800) Optical standards and testing; (170.1610) Clinical applications; (170.3880) Medical and biological imaging; (170.6510) Spectroscopy, tissue diagnostics
16.  Quality Assurance of Clinical MRI Scanners Using ACR MRI Phantom: Preliminary Results 
Journal of Digital Imaging  2004;17(4):279-284.
Clinical magnetic resonance imaging (MRI) scanners play an important role in the diagnosis of diseases and management of patient treatment. Quality assurance (QA) of the clinical MRI scanners is mandatory to obtain optimal images in a modern hospital. In this report, the phantom test for the American College of Radiology (ACR) MRI accreditation is used as the essential part of the MRI QA protocols. Seven important assessments of MR image quality are included as follows: geometric accuracy, high-contrast resolution, slice thickness accuracy, slice position accuracy, image intensity uniformity, percent signal ghosting, and low-contrast object detectability. In addition, signal-to-noise ratio and central frequency are monitored as well. The MRI QA procedures were applied to four clinical MRI scanners in our institute twice within 3 months. According to the QA results, the service engineers were more efficient in solving scanners problems when the ACR phantom test was run.
PMCID: PMC3047180  PMID: 15692871
MRI; quality assurance; ACR; phantom; image quality
17.  The Agreement between Competing Imaging Measures of Response of Hepatocellular Carcinoma to Yttrium-90 Radioembolization 
There are currently at least 6 major competing criteria that are used to determine response to 90Y and other liver-directed therapies including: a) RECIST, b) WHO, c) volumetric, d) 2D EASL, e) 3D EASL, f) functional diffusion weighted (DW) MR imaging. Our purpose was to evaluate the agreement between these competing tumor response classification schemes based on quantitative measurements of tumor size, necrosis, and changes in water mobility.
In this retrospective study, 20 HCC patients underwent 90Y radioembolization. The patients’ tumor burden before and 3–6 months after treatment was assessed with MRI. The percent change in size of tumors was used to classify patients into response categories. Kappa and agreement statistics were used to compare the concordance between the different criteria.
Conventional size criteria (RECIST, WHO, and volumetric) all had a substantial level of agreement (kappa statistics from 0.76 to 0.78) when classifying patients into response categories. However, the conventional size criteria in relation to either 2D or 3D EASL had only slight to moderate concurrence with kappa statistics as low as 0.06. 2D EASL criteria and functional DW MR imaging resulted in the highest response rates, 11/20 (55%) and 15/20 (75%) respectively, while conventional size criteria produced lower response rates.
Classification of HCC response to 90Y radioembolization was related to which of the competing criteria are used. We recommend that anatomic imaging criteria be used as the primary method to determine response and functional imaging criteria be used as a complementary secondary method.
PMCID: PMC2847083  PMID: 20172741
18.  Non-Invasive Imaging for Studying Anti-Angiogenic Therapy Effects 
Thrombosis and haemostasis  2013;109(3):10.1160/TH12-10-0721.
Noninvasive imaging plays an emerging role in preclinical and clinical cancer research and has high potential to improve clinical translation of new drugs. This article summarizes and discusses tools and methods to image tumor angiogenesis and monitor anti-angiogenic therapy effects. In this context, micro-computed tomography (μCT) is recommended to visualize and quantify the micro-architecture of functional tumor vessels. Contrast-enhanced ultrasound (US) and magnetic resonance imaging (MRI) are favorable tools to assess functional vascular parameters, such as perfusion and relative blood volume. These functional parameters have been shown to indicate anti-angiogenic therapy response at an early stage, before changes in tumor size appear. For tumor characterization, the imaging of the molecular characteristics of tumor blood vessels, such as receptor expression, might have an even higher diagnostic potential and has been shown to be highly suitable for therapy monitoring as well. In this context, US using targeted microbubbles is currently evaluated in clinical trials as an important tool for the molecular characterization of the angiogenic endothelium. Other modalities, being preferably used for molecular imaging of vessels and their surrounding stroma, are photoacoustic imaging (PAI), near-infrared fluorescence optical imaging (OI), MRI, positron emission tomography (PET) and single photon emission computed tomography (SPECT). The latter two are particularly useful if very high sensitivity is needed, and/or if the molecular target is difficult to access. Carefully considering the pros and cons of different imaging modalities in a multimodal imaging setup enables a comprehensive longitudinal assessment of the (micro)morphology, function and molecular regulation of tumor vessels.
PMCID: PMC3810587  PMID: 23407722
angiogenesis; functional imaging; molecular imaging; vessel normalization; cancer therapy
19.  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
20.  Imaging-Based Tumor Treatment Response Evaluation: Review of Conventional, New, and Emerging Concepts 
Korean Journal of Radiology  2012;13(4):371-390.
Tumor response may be assessed readily by the use of Response Evaluation Criteria in Solid Tumor version 1.1. However, the criteria mainly depend on tumor size changes. These criteria do not reflect other morphologic (tumor necrosis, hemorrhage, and cavitation), functional, or metabolic changes that may occur with targeted chemotherapy or even with conventional chemotherapy. The state-of-the-art multidetector CT is still playing an important role, by showing high-quality, high-resolution images that are appropriate enough to measure tumor size and its changes. Additional imaging biomarker devices such as dual energy CT, positron emission tomography, MRI including diffusion-weighted MRI shall be more frequently used for tumor response evaluation, because they provide detailed anatomic, and functional or metabolic change information during tumor treatment, particularly during targeted chemotherapy. This review elucidates morphologic and functional or metabolic approaches, and new concepts in the evaluation of tumor response in the era of personalized medicine (targeted chemotherapy).
PMCID: PMC3384819  PMID: 22778559
Tumor response; Oncology; Response Evaluation Criteria in Solid Tumor; Response assessment
21.  Statistical analysis of IMRT dosimetry quality assurance measurements for local delivery guideline 
To establish our institutional guideline for IMRT delivery, we statistically evaluated the results of dosimetry quality assurance (DQA) measurements and derived local confidence limits using the concept confidence limit of |mean|+1.96σ.
Materials and methods
From June 2006 to March 2009, 206 patients with head and neck cancer, prostate cancer, liver cancer, or brain tumor were treated using LINAC-based IMRT technique. In order to determine site specific DQA tolerances at a later stage, a hybrid plan with the same fluence maps as in the treatment plan was generated on CT images of a cylindrical phantom of acryl. Points of measurement using a 0.125 cm3 ion-chamber were typically located in the region of high and uniform doses. The planar dose distributions perpendicular to the central axis were measured by using a diode array in solid water with all fields delivered, and assessed using gamma criteria of 3%/3 mm. The mean values and standard deviations were used to develop the local confidence and tolerance limits. The dose differences and gamma pass rates for the different treatment sites were also evaluated in terms of total monitor uints (MU), MU/cGy, and the number of PTV's pieces.
The mean values and standard deviations of ion-chamber dosimetry differences between calculated and measured doses were -1.6 ± 1.2% for H&N cancer, -0.4 ± 1.2% for prostate and abdominal cancer, and -0.6 ± 1.5% for brain tumor. Most of measured doses (92.2%) agreed with the calculated doses within a tolerance limit of ±3% recommended in the literature. However, we found some systematic under-dosage for all treatment sites. The percentage of points passing the gamma criteria, averaged over all treatment sites was 97.3 ± 3.7%. The gamma pass rate and the agreement of ion-chamber dosimetry generally decreased with increasing the number of PTV's pieces, the degree of modulation (MU/cGy), and the total MU beyond 700. Our local confidence limits were comparable to those of AAPM TG 119 and ESTRO guidelines that were provided as a practical baseline for center-to-center commissioning comparison. Thus, our institutional confidence and action limits for IMRT delivery were set into the same levels of those guidelines.
Discussion and Conclusions
The systematic under-dosage were corrected by tuning up the MLC-related factors (dosimetric gap and transmission) in treatment planning system (TPS) and further by incorporating the tongue-and groove effect into TPS. Institutions that have performed IMRT DQA measurements over a certain period of time need to analyze their accrued DQA data. We confirmed the overall integrity of our IMRT system and established the IMRT delivery guideline during this procedure. Dosimetric corrections for the treatment plans outside of the action level can be suggested only with such rigorous DQA and statistical analysis.
PMCID: PMC3073875  PMID: 21439096
22.  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
23.  Assessment of Spectral Doppler in Preclinical Ultrasound Using a Small-Size Rotating Phantom 
Ultrasound in Medicine & Biology  2013;39(8):1491-1499.
Preclinical ultrasound scanners are used to measure blood flow in small animals, but the potential errors in blood velocity measurements have not been quantified. This investigation rectifies this omission through the design and use of phantoms and evaluation of measurement errors for a preclinical ultrasound system (Vevo 770, Visualsonics, Toronto, ON, Canada). A ray model of geometric spectral broadening was used to predict velocity errors. A small-scale rotating phantom, made from tissue-mimicking material, was developed. True and Doppler-measured maximum velocities of the moving targets were compared over a range of angles from 10° to 80°. Results indicate that the maximum velocity was overestimated by up to 158% by spectral Doppler. There was good agreement (<10%) between theoretical velocity errors and measured errors for beam-target angles of 50°–80°. However, for angles of 10°–40°, the agreement was not as good (>50%). The phantom is capable of validating the performance of blood velocity measurement in preclinical ultrasound.
PMCID: PMC3839405  PMID: 23711503
Blood velocity; Doppler ultrasound; High-frequency ultrasound; Doppler phantom; Preclinical ultrasound
24.  Robotic system for MRI-guided prostate biopsy: feasibility of teleoperated needle insertion and ex vivo phantom study 
Magnetic Resonance Imaging (MRI) combined with robotic assistance has the potential to improve on clinical outcomes of biopsy and local treatment of prostate cancer.
We report the workspace optimization and phantom evaluation of a five Degree of Freedom (DOF) parallel pneumatically actuated modular robot for MRI-guided prostate biopsy. To shorten procedure time and consequently increase patient comfort and system accuracy, a prototype of a MRI-compatible master–slave needle driver module using piezo motors was also added to the base robot.
Variable size workspace was achieved using appropriate link length, compared with the previous design. The 5-DOF targeting accuracy demonstrated an average error of 2.5mm (STD=1.37mm) in a realistic phantom inside a 3T magnet with a bevel-tip 18G needle. The average position tracking error of the master–slave needle driver was always below 0.1mm.
Phantom experiments showed sufficient accuracy for manual prostate biopsy. Also, the implementation of teleoperated needle insertion was feasible and accurate. These two together suggest the feasibility of accurate fully actuated needle placement into prostate while keeping the clinician supervision over the task.
PMCID: PMC3356244  PMID: 21698389
Transperineal prostate biopsy; MRI compatible; Pneumatic robot; Teleoperation; Accuracy evaluation; Phantom study
25.  Automatic Detection of Diabetic Retinopathy and Age-Related Macular Degeneration in Digital Fundus Images 
This article presents an algorithm that automatically classifies retinal images presenting with diabetic retinopathy and age-related macular degeneration. High sensitivity and specificity were achieved for the detection of both eye diseases.
To describe and evaluate the performance of an algorithm that automatically classifies images with pathologic features commonly found in diabetic retinopathy (DR) and age-related macular degeneration (AMD).
Retinal digital photographs (N = 2247) of three fields of view (FOV) were obtained of the eyes of 822 patients at two centers: The Retina Institute of South Texas (RIST, San Antonio, TX) and The University of Texas Health Science Center San Antonio (UTHSCSA). Ground truth was provided for the presence of pathologic conditions, including microaneurysms, hemorrhages, exudates, neovascularization in the optic disc and elsewhere, drusen, abnormal pigmentation, and geographic atrophy. The algorithm was used to report on the presence or absence of disease. A detection threshold was applied to obtain different values of sensitivity and specificity with respect to ground truth and to construct a receiver operating characteristic (ROC) curve.
The system achieved an average area under the ROC curve (AUC) of 0.89 for detection of DR and of 0.92 for detection of sight-threatening DR (STDR). With a fixed specificity of 0.50, the system's sensitivity ranged from 0.92 for all DR cases to 1.00 for clinically significant macular edema (CSME).
A computer-aided algorithm was trained to detect different types of pathologic retinal conditions. The cases of hard exudates within 1 disc diameter (DD) of the fovea (surrogate for CSME) were detected with very high accuracy (sensitivity = 1, specificity = 0.50), whereas mild nonproliferative DR was the most challenging condition (sensitivity= 0.92, specificity = 0.50). The algorithm was also tested on images with signs of AMD, achieving a performance of AUC of 0.84 (sensitivity = 0.94, specificity = 0.50).
PMCID: PMC3176039  PMID: 21666234

Results 1-25 (995217)