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.
small animal imaging; PET/CT; iodine-124; quantitative imaging
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.
Computed tomography (CT); Quality assurance; Image quality; Phantoms
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.
diffusion; MRI; phantom; ice water; quality control
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.
functional imaging; magnetic resonance imaging; positron emission tomography; signal transduction inhibitors; contrast enhanced imaging; personalized medicine
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.
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.
MRI; quality assurance; ACR; phantom; image quality
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.
(350.4800) Optical standards and testing; (170.1610) Clinical applications; (170.3880) Medical and biological imaging; (170.6510) Spectroscopy, tissue diagnostics
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.
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.
Magnetic resonance; quality assurance; pediatric brain tumor; American College of Radiology
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.
Targeted therapy; Tumor response assessment; Response criteria; Guideline; Non-small cell lung cancer; Dual energy CT
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.
Mouse models; Radiotherapy; Image guidance; MicroCT
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).
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.
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.
Cardiac and Neurovascular phantom; NEMA XR21; digital angiography phantom; digital subtracted angiography phantom
The field of cancer vaccines is currently in an active state of preclinical and clinical investigations. While no therapeutic cancer vaccine has to date been approved by the FDA, several new paradigms are emerging from recent clinical findings in both the use of combination therapy approaches and, perhaps more importantly, in clinical trial design and endpoint analyses. This paper will review recent clinical trials involving several different cancer vaccines from which data are emerging contrasting classical “tumor response” (RECIST) criteria with “patient response” in the manifestation of increased patient survival post-vaccine therapy. Also described are several strategies in which cancer vaccines can be exploited in combination with other agents and therapeutic modalities that are quite unique when compared with “conventional” combination therapies. This is most likely due to the phenomena that (a) cancer vaccines initiate a dynamic immune process that can be exploited in subsequent therapies, and (b) both radiation and certain chemotherapeutic agents have been shown to alter the phenotype of tumor cells as to render them more susceptible to T-cell–mediated killing. Consequently, evidence is emerging from several studies in which patient cohorts who first receive a cancer vaccine (as contrasted with control cohorts) benefit clinically from subsequent therapies.
cancer vaccines; immunotherapy; combination therapy; prostate cancer
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.
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.
Targeted therapy; Tumor response assessment; Response criteria; Guideline, Non-small cell lung cancer
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.
Medical robotics; Needle insertion; Radiofrequency ablation (RFA); Haptic feedback; Continuous MRI imaging; Teleoperation
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.
While Magnetic Resonance Thermometry (MRT) has been extensively utilized for non-invasive temperature measurement, there is limited data on the use of high field (≥7T) scanners for this purpose. MR-guided Focused Ultrasound (MRgFUS) is a promising non-invasive method for localized hyperthermia and drug delivery. MRT based on the temperature sensitivity of the proton resonance frequency (PRF) has been implemented in both a tissue phantom and in vivo in a mouse Met-1 tumor model, using partial parallel imaging (PPI) to speed acquisition. An MRgFUS system capable of delivering a controlled 3D acoustic dose during real time MRT with proportional, integral, and derivative (PID) feedback control was developed and validated. Real-time MRT was validated in a tofu phantom with fluoroptic temperature measurements, and acoustic heating simulations were in good agreement with MR temperature maps. In an in vivo Met-1 mouse tumor, the real-time PID feedback control is capable of maintaining the desired temperature with high accuracy. We found that real time MR control of hyperthermia is feasible at high field, and k-space based PPI techniques may be implemented for increasing temporal resolution while maintaining temperature accuracy on the order of 1°C.
Solid water is often the phantom material of choice for dosimetry procedures in radiotherapy high-energy X-ray and electron beam radiation calibration and quality assurance. This note investigates variation in heat conduction that can occur for a common commercially available solid water stack phantom when a temperature differential occurs between the phantom and ambient temperature. These variations in temperature can then affect radiation measurements and thus the accuracy of radiation dosimetry. In this manuscript, we aim to investigate the variations in temperature which can occur in radiation measurement incorporated (RMI) solid water phantoms, their thermal properties and the effects on radiation dosimetry which can occur because of temperature differentials. Results have shown that the rate of temperature change at a phantom center is a complex function but appears relatively proportional to the surface area of the phantom in normal clinical usage. It is also dependent on the thermal conductivity of any material in contact with the phantom; and the nature of the phantom construction, i.e., the number and thickness of slices within the phantom. A thermal time constant of approximately 20 min was measured for a 2-cm solid water phantom slice when located on a steel workbench in comparison to 60 min when located on a wooden workbench (linac couch insert). It is found that for larger solid water stack phantoms, a transient (within 1°C) thermal equilibrium exists at the center for up to 2 h, before the temperature begins to change. This is assumed to be due to the insulating properties of multiple slices within the stack, whereby very small air spaces are introduced inhibiting the heat conduction through the phantom material. It is therefore recommended that the solid water/phantom material is kept within the treatment room for closest thermal accuracy conditions or at least placed within the room approximately 10 h before dosimetry measurements. If these options are not available, a standard linear interpolation method for calculation of temperature should be used to minimize uncertainty of temperature measurements.
Dosimetry; heat conduction; radiotherapy
This study presents a new multimodal imaging approach that includes high-frequency ultrasound, fluorescence intensity, confocal, and spectral imaging to improve the preclinical evaluation of new therapeutics in vivo. Here we use this approach to assess in vivo the therapeutic efficacy of the novel chemotherapy construct, HerDox during and after treatment. HerDox is comprised of doxorubicin non-covalently assembled in a viral-like particle targeted to HER2+ tumor cells, causing tumor cell death at over 10-fold lower dose compared to the untargeted drug, while sparing the heart. Whereas our initial proof-of-principle studies on HerDox used tumor growth/shrinkage rates as a measure of therapeutic efficacy, here we show that multimodal imaging deployed during and after treatment can supplement traditional modes of tumor monitoring to further characterize the particle in tissues of treated mice. Specifically, we show here that tumor cell apoptosis elicited by HerDox can be monitored in vivo during treatment using high frequency ultrasound imaging, while in situ confocal imaging of excised tumors shows that HerDox indeed penetrated tumor tissue and can be detected at the subcellular level, including in the nucleus, via Dox fluorescence. In addition, ratiometric spectral imaging of the same tumor tissue enables quantitative discrimination of HerDox fluorescence from autofluorescence in situ. In contrast to standard approaches of preclinical assessment, this new method provides multiple/complementary information that may shorten the time required for initial evaluation of in vivo efficacy, thus potentially reducing the time and cost for translating new drug molecules into the clinic.
Cervical lymph nodes are common sites of metastatic involvement in head and neck cancers. These lymph nodes are superficially located and palpation is a common practice for assessing nodal hardness and staging cancer which is, however, too subjective and with limited accuracy. In this study, the mechanical properties of pig lymph node tissues were investigated using ultrasound elastography and indentation test. Lymph nodes were excised from fresh pork pieces and embedded in an agar-gelatin phantom for strain imaging by elastography. A strain ratio reflecting the strain contrast of lymph node over agar-gelatin phantom was used to assess the elasticity of the lymph node. A cutting device was then custom-designed to slice the phantom into uniform slices for indentation test. The measurements revealed that there were significant differences in both the strain ratio and Young’s modulus between the peripheral and middle regions of the lymph nodes (both p < 0.05); however, the results appeared contradictory. Correlation between the results of the two measurements (modulus ratio vs. inversed strain ratio) showed their association was moderate for both the peripheral and middle regions (R2 = 0.437 and 0.424 respectively). As the tests were only performed on normal lymph nodes, comparison in stiffness between healthy and abnormal lymph nodes could not be made. Future studies should be conducted to quantify the stiffness change in abnormal lymph nodes.
Ultrasound; elastography; indentation; lymph node; soft tissue; strain image; young’s modulus.
The commercially available X-ray fluoroscopy quality assurance phantom, the Leeds test object TOR18FG, was found to be suitable to assess T-ray image quality in the range (0.1-0.4) THz at a depth of 0.5 cm. Previous to this only custom made phantoms, made especially for the T-ray region, assessed T-ray spatial resolution. However, if sub-wavelength techniques are used, the Leeds test phantom may be implemented to measure the T-ray systems spatial resolution, allowing us to directly compare X-ray and T-ray spatial resolution. The systems compared include a Gulmay Orthovoltage machine (X-ray), the On Board Imager (OBI) of a Varian linear accelerator (X-ray), a two-colour system (T-ray) and Terahertz Time Domain Spectroscopy (THz-TDS) system. X-rays were found to have a spatial resolution of 1.25 lp/mm using the On Board Imager of a Varian Linear Accelerator whilst T-rays imaged using a broadband source imaged through a spatial pinhole had a spatial resolution of 0.56 lp/mm. The TOR18FG background material was found to block, 90% and 99% of the broadband T-rays emitted from a THz-TDS photo-conductive emitter, at 0.4 THz and 0.53 THz respectively. Contrast sensitivity was found to be 3% for 25 cm × 25 cm X-ray field at 65 kV, whilst this value could not be established for T-rays using the TOR18FG. All contrast circles were found to be the same for T-rays i.e. all 40% at 0.1 THz. Images of the same leaf were taken with diagnostic X-rays and both broadband and continuous wave (CW) T-ray systems. T-rays proved superior in providing image contrast, for a hydrated leaf, over X-rays.
Terahertz; X-ray; imaging; resolution
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.
Compared to conventional piezoelectric transducers, new capacitive microfabricated ultrasonic transducer (CMUT) technology is expected to offer a broader bandwidth, higher resolution and advanced 3D/4D imaging inherent in a 2D array. For ultrasound scatterer size imaging, a broader frequency range provides more information on frequency-dependent backscatter, and therefore, generally more accurate size estimates. Elevational compounding, which can significantly reduce the large statistical fluctuations associated with parametric imaging, becomes readily available with a 2D array. In this work, we show phantom and in vivo breast tumor scatterer size image results using a prototype 2D CMUT transducer (9 MHz center frequency) attached to a clinical scanner. A uniform phantom with two 1 cm diameter spherical inclusions of slightly smaller scatterer size was submerged in oil and scanned by both the 2D CMUT and a conventional piezoelectric linear array transducer. The attenuation and scatterer sizes of the sample were estimated using a reference phantom method. RF correlation analysis was performed using the data acquired by both transducers. The 2D CMUT results indicate that at a 2 cm depth (near the transmit focus for both transducers) the correlation coefficient reduced to less than 1/e for 0.2 mm lateral or 0.25 mm elevational separation between acoustic scanlines. For the conventional array this level of decorrelation requires a 0.3 mm lateral or 0.75 mm elevational translation. Angular and/or elevational compounding is used to reduce the variance of scatterer size estimates. The 2D array transducer acquired RF signals from 140 planes over a 2.8 cm elevational direction. If no elevational compounding is used, the fractional standard deviation of the size estimates is about 12% of the mean size estimate for both the spherical inclusion and the background. Elevational compounding of 11 adjacent planes reduces it to 7% for both media. Using an experimentally estimated attenuation of 0.6 dB cm−1MHz−1, scatterer size estimates for an in vivo breast tumor also demonstrate improvements using elevational compounding with data from the 2D CMUT transducer.