Accuracy and reproducibility of tumor positioning during prolonged and multi-modality animal imaging studies

Zhang, Mutian; Huang, Minming; Le, Carl; Zanzonico, Pat; Claus, Filip; Kolbert, Katherine S.; Martin, Kyle S.; Ling, C. Clifton; Koutcher, Jason A.; Humm, John L.

doi:10.1088/0031-9155/53/20/021

Cited by 23 publications

(25 citation statements)

References 26 publications

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“…Recent data from our laboratory, applicable in part to this study, indicated that an uncertainty of 0.8 mm in repositioning the tumor in serial and prolonged imaging studies. 48 In this study, the possible bending of the Oxylite probe in penetrating the tumor may have introduced additional spatial uncertainty, although care was taken to reposition the probe if obvious bending was observed.…”

Section: Discussionmentioning

confidence: 97%

A robotic system for ‐FMISO PET‐guided intratumoral measurements

et al. 2009

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An image-guided robotic system was used to measure the oxygen tension (pO2) in rodent tumor xenografts using interstitial probes guided by tumor hypoxia PET images. Rats with approximately 1 cm diameter tumors were anesthetized and immobilized in a custom-fabricated whole-body mold. Imaging was performed using a dedicated small-animal PET scanner (R4 or Focus 120 microPET) approximately 2 h after the injection of the hypoxia tracer 18F-fluoromisonidazole (18F-FMISO). The coordinate systems of the robot and PET were registered based on fiducial markers in the rodent bed visible on the PET images. Guided by the 3D microPET image set, measurements were performed at various locations in the tumor and compared to the corresponding 18F-FMISO image intensity at the respective measurement points. Experiments were performed on four tumor-bearing rats with 4 (86), 3 (80), 7 (162), and 8 (235) measurement tracks (points) for each experiment. The 18F-FMISO image intensities were inversely correlated with the measured pO2, with a Pearson coefficient ranging from -0.14 to -0.97 for the 22 measurement tracks. The cumulative scatterplots of pO2 versus image intensity yielded a hyperbolic relationship, with correlation coefficients of 0.52, 0.48, 0.64, and 0.73, respectively, for the four tumors. In conclusion, PET image-guided pO2 measurement is feasible with this robot system and, more generally, this system will permit point-by-point comparison of physiological probe measurements and image voxel values as a means of validating molecularly targeted radiotracers. Although the overall data fitting suggested that 18F-FMISO may be an effective hypoxia marker, the use of static 18F-FMISO PET postinjection scans to guide radiotherapy might be problematic due to the observed high variation in some individual data pairs from the fitted curve, indicating potential temporal fluctuation of oxygen tension in individual voxels or possible suboptimal imaging time postadministration of hypoxia-related trapping of 18F-FMISO.

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Section: Discussionmentioning

confidence: 97%

A robotic system for ‐FMISO PET‐guided intratumoral measurements

et al. 2009

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“…To make the MR-IGRT work in vivo, subject immobilisation throughout the whole procedure is crucial as accurate registration of MRI-to-CT images will depend on the magnitude of intra- and/or inter-scan displacements [10, 13]. To minimise the effects of these an MR- and CBCT-compatible animal support cradle was developed.…”

Section: Discussionmentioning

confidence: 99%

An efficient and robust MRI-guided radiotherapy planning approach for targeting abdominal organs and tumours in the mouse

Kersemans¹,

Beech²,

Gilchrist³

et al. 2017

PLoS ONE

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IntroductionPreclinical CT-guided radiotherapy platforms are increasingly used but the CT images are characterized by poor soft tissue contrast. The aim of this study was to develop a robust and accurate method of MRI-guided radiotherapy (MR-IGRT) delivery to abdominal targets in the mouse.MethodsA multimodality cradle was developed for providing subject immobilisation and its performance was evaluated. Whilst CT was still used for dose calculations, target identification was based on MRI. Each step of the radiotherapy planning procedure was validated initially in vitro using BANG gel dosimeters. Subsequently, MR-IGRT of normal adrenal glands with a size-matched collimated beam was performed. Additionally, the SK-N-SH neuroblastoma xenograft model and the transgenic KPC model of pancreatic ductal adenocarcinoma were used to demonstrate the applicability of our methods for the accurate delivery of radiation to CT-invisible abdominal tumours.ResultsThe BANG gel phantoms demonstrated a targeting efficiency error of 0.56 ± 0.18 mm. The in vivo stability tests of body motion during MR-IGRT and the associated cradle transfer showed that the residual body movements are within this MR-IGRT targeting error. Accurate MR-IGRT of the normal adrenal glands with a size-matched collimated beam was confirmed by γH2AX staining. Regression in tumour volume was observed almost immediately post MR-IGRT in the neuroblastoma model, further demonstrating accuracy of x-ray delivery. Finally, MR-IGRT in the KPC model facilitated precise contouring and comparison of different treatment plans and radiotherapy dose distributions not only to the intra-abdominal tumour but also to the organs at risk.ConclusionThis is, to our knowledge, the first study to demonstrate preclinical MR-IGRT in intra-abdominal organs. The proposed MR-IGRT method presents a state-of-the-art solution to enabling robust, accurate and efficient targeting of extracranial organs in the mouse and can operate with a sufficiently high throughput to allow fractionated treatments to be given.

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“…Dual imaging approaches combine the advantages of each modality (for example the soft-tissue contrast of MR and guidance capabilities of CT), but require additional instrumentation and complex logistics. Our group has studied issues of animal image registration procedures in detail (27); such a technique requires the mouse to be immobilized from the start of the MR to the end of radiation treatment. In the context of more difficult to identify GEMM disease, our method still provides soft-tissue structure contrast using CT.…”

Section: Discussionmentioning

confidence: 99%

Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models

Thorek¹,

Kramer

Chen³

et al. 2015

International Journal of Radiation Oncology*Biology*Physics

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Purpose To evaluate the feasibility of delivering experimental radiotherapy to tumors in the mouse pancreas. Imaging and treatment were performed using combined CT (computed tomography)/orthovoltage treatment with a rotating gantry. Methods and Materials After intraperitoneal administration of radiopaque iodinated contrast, abdominal organ delineation was performed by X-ray CT. With this technique we delineated the pancreas, and both orthotopic xenografts and genetically engineered disease. CT imaging was validated by comparison with magnetic resonance (MR) imaging. Therapeutic radiation was delivered via a 1 cm diameter field. Selective X-ray radiation therapy (XRT) of the non-invasively defined orthotopic mass was confirmed using γH2AX staining. Mice could tolerate a dose of 15 Gy when the field was centered on the pancreas tail, and treatment was delivered as a continuous 360-degree arc. This strategy was then used for radiation therapy planning for selective delivery of therapeutic XRT to orthotopic tumors. Results Tumor growth delay after 15 Gy was monitored, using CT and ultrasound to determine the tumor volume at various times post-treatment. Our strategy enables the use of clinical radiation oncology approaches to treat experimental tumors in the pancreas of small animals for the first time. We demonstrate that delivery of 15 Gy from a rotating gantry minimizes background healthy tissue damage and significantly retards tumor growth. Conclusions This advance permits evaluation of radiation planning and dosing parameters. Accurate non-invasive longitudinal imaging and monitoring of tumor progression and therapeutic response in pre-clinical models is now possible, and can be expected to more effectively evaluate pancreatic cancer disease and therapeutic response.

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Accuracy and reproducibility of tumor positioning during prolonged and multi-modality animal imaging studies

Cited by 23 publications

References 26 publications

A robotic system for ‐FMISO PET‐guided intratumoral measurements

A robotic system for ‐FMISO PET‐guided intratumoral measurements

An efficient and robust MRI-guided radiotherapy planning approach for targeting abdominal organs and tumours in the mouse

Reverse-Contrast Imaging and Targeted Radiation Therapy of Advanced Pancreatic Cancer Models

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