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Preclinical multimodality phantom design for quality assurance of tumor size measurement
Yongsook C Lee, Gary D Fullerton, Cristel Baiu, Margaret G Lescrenier, Beth A Goins
BMC Medical Physics , 2011, DOI: 10.1186/1756-6649-11-1
Abstract: Three phantoms (Gammex/UTHSCSA Mark 1, Gammex/UTHSCSA Mark 2 and UTHSCSA multimodality tumor measurement phantom) containing tumor-simulating test objects were designed and constructed. All three phantoms were scanned in US, CT and MRI devices. The size of test objects in the phantoms was measured from the US, CT and MRI images. RECIST, WHO and volume analyses were performed.The smaller phantom size, simplified design and better test object CT contrast of the UTHSCSA multimodality tumor measurement phantom allowed scanning of the phantom in preclinical US, CT and MRI scanners compared with only limited preclinical scanning capability of Mark 1 and Mark 2 phantoms. For all imaging modalities, RECIST and WHO errors were reduced for UTHSCSA multimodality tumor measurement phantom (≤1.69 ± 0.33%) compared with both Mark 1 (≤ -7.56 ± 6.52%) and Mark 2 (≤ 5.66 ± 1.41%) phantoms. For the UTHSCSA multimodality tumor measurement phantom, measured tumor volumes were highly correlated with NIST traceable design volumes for US (R2 = 1.000, p < 0.0001), CT (R2 = 0.9999, p < 0.0001) and MRI (R2 = 0.9998, p < 0.0001).The UTHSCSA multimodality tumor measurement phantom described in this study can potentially be a useful quality assurance tool for verifying radiologic assessment of tumor size change during preclinical anti-cancer therapy testing with multiple imaging modalities.Highly consistent, reproducible and standardized response criteria are essential to evaluate the efficacy of new anti-cancer drugs in multicenter trials [1]. The World Health Organization (WHO) criteria and the Response Evaluation Criteria in Solid Tumors (RECIST) have been widely used as the only imaging biomarker presently approved by the United States Food and Drug Administration (FDA) for drug testing, although the use of functional imaging methods such as Positron Emission Tomography (PET) Response Criteria in Solid Tumors (PERCIST) complements the limitations of anatomic methods in treatment response as
Multimodality Imaging In Vivo for Preclinical Assessment of Tumor-Targeted Doxorubicin Nanoparticles  [PDF]
Jae Youn Hwang, Jinhyoung Park, Bong Jin Kang, David J. Lubow, David Chu, Daniel L. Farkas, K. Kirk Shung, Lali K. Medina-Kauwe
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0034463
Abstract: 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.
Ultrasound Biomicroscopy in Small Animal Research: Applications in Molecular and Preclinical Imaging
A. Greco,M. Mancini,S. Gargiulo,M. Gramanzini,P. P. Claudio,A. Brunetti,M. Salvatore
Journal of Biomedicine and Biotechnology , 2012, DOI: 10.1155/2012/519238
Abstract: Ultrasound biomicroscopy (UBM) is a noninvasive multimodality technique that allows high-resolution imaging in mice. It is affordable, widely available, and portable. When it is coupled to Doppler ultrasound with color and power Doppler, it can be used to quantify blood flow and to image microcirculation as well as the response of tumor blood supply to cancer therapy. Target contrast ultrasound combines ultrasound with novel molecular targeted contrast agent to assess biological processes at molecular level. UBM is useful to investigate the growth and differentiation of tumors as well as to detect early molecular expression of cancer-related biomarkers in vivo and to monitor the effects of cancer therapies. It can be also used to visualize the embryological development of mice in uterus or to examine their cardiovascular development. The availability of real-time imaging of mice anatomy allows performing aspiration procedures under ultrasound guidance as well as the microinjection of cells, viruses, or other agents into precise locations. This paper will describe some basic principles of high-resolution imaging equipment, and the most important applications in molecular and preclinical imaging in small animal research.
Multimodality Imaging of Tumor Response to Doxil
Fan Zhang, Lei Zhu, Gang Liu, Naoki Hida, Guangming Lu, Henry S. Eden, Gang Niu, Xiaoyuan Chen
Theranostics , 2011,
Abstract: Purpose: Early assessment of tumor responses to chemotherapy could enhance treatment outcomes by ensuring that, from the beginning, treatments meet the individualized needs of patients. In this study, we applied multiple modality molecular imaging techniques to pre-clinical monitoring of early tumor responses to Doxil, focusing on imaging of apoptosis. Methods: Mice bearing UM-SCC-22B human head and neck squamous cancer tumors received either PBS or 1 to 2 doses of Doxil (doxorubicin HCl liposome injection) (10 mg/kg/dose). Bioluminescence signals from an apoptosis-responsive reporter gene were captured for apoptosis evaluation. Tumor metabolism and proliferation were assessed by 18F-FDG and 3'-18F-fluoro-3'-deoxythymidine (18F-FLT) positron emission tomography. Diffusion-weighted magnetic resonance imaging (DW-MRI) was performed to calculate averaged apparent diffusion coefficients (ADCs) for the whole tumor volume. After imaging, tumor samples were collected for histological evaluation, including terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), anti-CD31, and Ki-67 immunostaining. Results: Two doses of Doxil significantly inhibited tumor growth. Bioluminescence imaging (BLI) indicated apoptosis of tumor cells after just 1 dose of Doxil treatment, before apparent tumor shrinkage. 18F-FDG and 18F-FLT PET imaging identified decreased tumor metabolism and proliferation at later time points than those at which BLI indicated apoptosis. MRI measurements of ADC altered in response to Doxil, but only after tumors were treated with 2 doses. Decreased tumor proliferation and increased apoptotic cells were confirmed by changes of Ki-67 index and apoptotic ratio. Conclusion: Our study of tumor responses to different doses of Doxil demonstrated that it is essential to combine apoptosis imaging strategies with imaging of other critical biological or pathological pathways, such as metabolism and proliferation, to improve clinical decision making in apoptosis-related diseases and interventions.
Tumor delineation: The weakest link in the search for accuracy in radiotherapy  [cached]
Njeh C
Journal of Medical Physics , 2008,
Abstract: Radiotherapy is one of the most effective modalities for the treatment of cancer. However, there is a high degree of uncertainty associated with the target volume of most cancer sites. The sources of these uncertainties include, but are not limited to, the motion of the target, patient setup errors, patient movements, and the delineation of the target volume. Recently, many imaging techniques have been introduced to track the motion of tumors. The treatment delivery using these techniques is collectively called image-guided radiation therapy (IGRT). Ultimately, IGRT is only as good as the accuracy with which the target is known. There are reports of interobserver variability in tumor delineation across anatomical sites, but the widest ranges of variations have been reported for the delineation of head and neck tumors as well as esophageal and lung carcinomas. Significant interobserver variability in target delineation can be attributed to many factors including the impact of imaging and the influence of the observer (specialty, training, and personal bias). The visibility of the target can be greatly improved with the use of multimodality imaging by co-registration of CT with a second modality such as magnetic resonance imaging (MRI) and/or positron emission tomography. Also, continuous education, training, and cross-collaboration of the radiation oncologist with other specialties can reduce the degree of variability in tumor delineation.
An Efficient Technique of Multimodality Medical Image Fusion using Improved Contourlet Transformation
Jaspreet Kaur,,Chirag Sharma
International Journal of Innovative Technology and Exploring Engineering , 2012,
Abstract: In medical field to diagnosis the disease an advance technology is used that is multimodality images. To find best diagnosis for a particular disease we perform image fusion. Major issue in multimodality medical image fusion is how to fuse two or more images of different modalities, so that we get more accurate information. To perform efficient fusion contourlet transformation gives the up to mark results. So, In this paper, we propose an improved contourlet transformation, in which we are using multi scale decomposition and considering that DFBs can be modified with Log Gabor Filter in place of low pass and high pass filter. Log Gabor filter localizes an image more accurately and also minimizes the DC Component (noise in image) with which we are improving the quality of fused image. In this paper, we are considering Registered Medical Images. Performance of proposed method is evaluated by five qualities.
Flow Measurements in a Blood-Perfused Collagen Vessel Using X-Ray Micro-Particle Image Velocimetry  [PDF]
Elizabeth Antoine, Cara Buchanan, Kamel Fezzaa, Wah-Keat Lee, M. Nichole Rylander, Pavlos Vlachos
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081198
Abstract: Blood-perfused tissue models are joining the emerging field of tumor engineering because they provide new avenues for modulation of the tumor microenvironment and preclinical evaluation of the therapeutic potential of new treatments. The characterization of fluid flow parameters in such in-vitro perfused tissue models is a critical step towards better understanding and manipulating the tumor microenvironment. However, traditional optical flow measurement methods are inapplicable because of the opacity of blood and the thickness of the tissue sample. In order to overcome the limitations of optical method we demonstrate the feasibility of using phase-contrast x-ray imaging to perform microscale particle image velocimetry (PIV) measurements of flow in blood perfused hydrated tissue-representative microvessels. However, phase contrast x-ray images significantly depart from the traditional PIV image paradigm, as they have high intensity background, very low signal-to-noise ratio, and volume integration effects. Hence, in order to achieve accurate measurements special attention must be paid to the image processing and PIV cross-correlation methodologies. Therefore we develop and demonstrate a methodology that incorporates image preprocessing as well as advanced PIV cross-correlation methods to result in measured velocities within experimental uncertainty.
Application of Benchtop-magnetic resonance imaging in a nude mouse tumor model
Henrike Caysa, Hendrik Metz, Karsten M?der, Thomas Mueller
Journal of Experimental & Clinical Cancer Research , 2011, DOI: 10.1186/1756-9966-30-69
Abstract: We used a prototype of an in vivo BT-MRI apparatus to visualise organs and tumors and to analyse tumor progression in nude mouse xenograft models of human testicular germ cell tumor and colon carcinoma.Subcutaneous xenografts were easily identified as relative hypointense areas in transaxial slices of NMR images. Monitoring of tumor progression evaluated by pixel extension analyses based on NMR images correlated with increasing tumor volume calculated by calliper measurement. Gd-BOPTA contrast agent injection resulted in a better differentiation between parts of the urinary tissues and organs due to fast elimination of the agent via kidneys. In addition, interior structuring of tumors could be observed. A strong contrast enhancement within a tumor was associated with a central necrotic/fibrotic area.BT-MRI provides satisfactory image quality to visualize organs and tumors and to monitor tumor progression and structure in mouse models.MRI plays a key role in the preclinical development of new drugs, diagnostics and their delivery systems. However, very high installation and running cost of existing superconducting MRI machines limit the spread of the method. The new method of Benchtop-MRI (BT-MRI) has the potential to overcome this limitation due to much lower installation and almost no running costs. The lower quality of the NMR images is expected due to the low field strength and decreased magnet homogeneity. However, very recently we could show that BT-MRI is able to characterize floating mono- or bilayer tablets, osmotic controlled push-pull tablets [1-4] or scaffolds for tissue engineering in vitro [5]. A broad, important and increasing range of MRI applications are linked with preclinical studies on small rodents such as mice or rats [6-8]. Thereby, first developments and testing of more compact MRI systems have been reported [9,10]. In the present study we have tested a prototype of a new in vivo BT-MRI apparatus.Clearly, BT-MRI could overcome one of the curre
Multimodality Imaging of Abnormal Vascular Perfusion and Morphology in Preclinical 9L Gliosarcoma Model  [PDF]
Moses M. Darpolor,Robert C. Molthen,Kathleen M. Schmainda
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0016621
Abstract: This study demonstrates that a dynamic susceptibility contrast-magnetic resonance imaging (DSC-MRI) perfusion parameter may indicate vascular abnormality in a brain tumor model and reflects an effect of dexamethasone treatment. In addition, X-ray computed tomography (CT) measurements of vascular tortuosity and tissue markers of vascular morphology were performed to investigate the underpinnings of tumor response to dexamethasone.
Multimodality Medical Image Registration Based on Dividing Rectangles
基于Dividing Rectangles的多模态

ZHANG Jia-wan,LI Tan,SUN Ji-zhou,

中国图象图形学报 , 2008,
Abstract: A global optimization method based on mutual information is proposed for multimodality medical image registration. First external surfaces are extracted from various image modalities and the ICP algorithm is adopted to initially align unregistered images. Then the registration is performed by maximization of normalized mutual information using a deterministic global optimization algorithm named Dividing Rectangles. The surface based matching is used to provide a good start point for Dividing Rectangles in order to fully utilize its high efficiency in small search space. The results of experiment on three dimensional human brain data show that this method is accurate, fast, and avoids local minimums efficiently.
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