A Human-derived Dual MRI/PET Reporter Gene System with High Translational Potential for Cell Tracking

Purpose: Reporter gene imaging has been extensively used to longitudinally report on whole-body distribution and viability of transplanted engineered cells. Multi-modal cell tracking can provide complementary information on cell fate. Typical multi-modal reporter gene systems often combine clinical and preclinical modalities. A multi-modal reporter gene system for magnetic resonance imaging (MRI) and positron emission tomography (PET), two clinical modalities, would be advantageous by combining the sensitivity of PET with the high-resolution morphology and non-ionizing nature of MRI. Procedures: We developed and evaluated a dual MRI/PET reporter gene system composed of two human-derived reporter genes that utilize clinical reporter probes for engineered cell detection. As a proof-of-concept, breast cancer cells were engineered to co-express the human organic anion transporter polypeptide 1B3 (OATP1B3) that uptakes the clinical MRI contrast agent gadolinium ethoxybenzyl-diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), and the human sodium iodide symporter (NIS) which uptakes the PET tracer, [18F] tetrafluoroborate ([18F] TFB). Results: T1-weighted MRI results in mice exhibited significantly higher MRI signals in reporter-gene-engineered mammary fat pad tumors versus contralateral naïve tumors (p \u3c 0.05). No differences in contrast enhancement were observed at 5 h after Gd-EOB-DTPA administration using either intravenous or intraperitoneal injection. We also found significantly higher standard uptake values (SUV) in engineered tumors in comparison to the naïve tumors in [18F]TFB PET images (p \u3c 0.001). Intratumoral heterogeneity in signal enhancement was more conspicuous in relatively higher resolution MR images compared to PET images. Conclusions: Our study demonstrates the ability to noninvasively track cells engineered with our human-derived dual MRI/PET reporter system, enabling a more comprehensive evaluation of transplanted cells. Future work is focused on applying this tool to track therapeutic cells, which may one day enable the broader application of cell tracking within the healthcare system

Comparative study on the detection of early dental caries using thermo-photonic lock-in imaging and optical coherence tomography

Early detection of dental caries is known to be the key to the effectiveness of therapeutic and preventive approaches in dentistry. However, existing clinical detection techniques, such as radiographs, are not sufficiently sensitive to detect and monitor the progression of caries at early stages. As such, in recent years, several optics-based imaging modalities have been proposed for the early detection of caries. The majority of these techniques rely on the enhancement of light scattering in early carious lesions, while a few of them are based on the enhancement of light absorption at early caries sites. In this paper, we report on a systemic comparative study on the detection performances of optical coherence tomography (OCT) and thermophotonic lock-in imaging (TPLI) as representative early caries detection modalities based on light scattering and absorption, respectively. Through controlled demineralization studies on extracted human teeth and µCT validation experiments, several detection performance parameters of the two modalities such as detection threshold, sensitivity and specificity have been qualitatively analyzed and discussed. Our experiment results suggests that both modalities have sufficient sensitivity for the detection of well-developed early caries on occlusal and smooth surfaces; however, TPLI provides better sensitivity and detection threshold for detecting very early stages of caries formation, which is deemed to be critical for the effectiveness of therapeutic and preventive approaches in dentistry. Moreover, due to the more specific nature of the light absorption contrast mechanism over light scattering, TPLI exhibits better detection specificity, which results in less false positive readings and thus allows for the proper differentiation of early caries regions from the surrounding intact areas. The major shortcoming of TPLI is its inherent depth-integrated nature, prohibiting the production of depth-resolved/B-mode like images. The outcomes of this research justify the need for a light-absorption based imaging modality with the ability to produce tomographic and depth-resolved images, combining the key advantages of OCT and TPLI.York University Librarie

Pharmacokinetic Analysis of Gd-DTPA Enhancement in dynamic three-dimensional MRI of breast lesions

The purpose of this study was to demonstrate that dynamic MRI covering both breasts can provide sensitivity for tumor detection as well as specificity and sensitivity for differentiation of tumor malignancy. Three-dimensional gradient echo scans were used covering both breasts. Before Gd-DTPA bolus injection, two scans were obtained with different flip angles, and after injection, a dynamic series followed. Thirty-two patients were scanned according to this protocol. From these scans, in addition to enhancement, the value of T1 before injection was obtained. This was used to estimate the concentration of Gd-DTPA as well as the pharmacokinetic parameters governing its time course. Signal enhancement in three-dimensional dynamic scanning was shown to be a sensitive basis for detection of tumors. In our series, all but two mam-mographically suspicious lesions did enhance, and in three cases, additional enhancing lesions were found, two of which were in the contralateral breast. The parameter most suited for classification of breast lesions into benign or malignant was shown to be the pharmacokinetically defined permeability k31, which, for that test, gave a sensitivity of 92% and a specificity of 70%. Our three-dimensional dynamic MRI data are sensitive for detection of mammographically occult breast tumors and specific for classification of these as benign or malignant

The Integration of Positron Emission Tomography With Magnetic Resonance Imaging

A number of laboratories and companies are currently exploring the development of integrated imaging systems for magnetic resonance imaging (MRI) and positron emission tomography (PET). Scanners for both preclinical and human research applications are being pursued. In contrast to the widely distributed and now quite mature PET/computed tomography technology, most PET/MRI designs allow for simultaneous rather than sequential acquisition of PET and MRI data. While this offers the possibility of novel imaging strategies, it also creates considerable challenges for acquiring artifact-free images from both modalities. This paper discusses the motivation for developing combined PET/MRI technology, outlines the obstacles in realizing such an integrated instrument, and presents recent progress in the development of both the instrumentation and of novel imaging agents for combined PET/MRI studies. The performance of the first-generation PET/MRI systems is described. Finally, a range of possible biomedical applications for PET/MRI are outlined

High dynamic range imaging for archaeological recording

This paper notes the adoption of digital photography as a primary recording means within archaeology, and reviews some issues and problems that this presents. Particular attention is given to the problems of recording high-contrast scenes in archaeology and High Dynamic Range imaging using multiple exposures is suggested as a means of providing an archive of high-contrast scenes that can later be tone-mapped to provide a variety of visualisations. Exposure fusion is also considered, although it is noted that this has some disadvantages. Three case studies are then presented (1) a very high contrast photograph taken from within a rock-cut tomb at Cala Morell, Menorca (2) an archaeological test pitting exercise requiring rapid acquisition of photographic records in challenging circumstances and (3) legacy material consisting of three differently exposed colour positive (slide) photographs of the same scene. In each case, HDR methods are shown to significantly aid the generation of a high quality illustrative record photograph, and it is concluded that HDR imaging could serve an effective role in archaeological photographic recording, although there remain problems of archiving and distributing HDR radiance map data

Clinical utility of gadobenate dimeglumine in contrast-enhanced MRI of the breast: a review

Breast magnetic resonance imaging (MRI) is considered the technique with the highest sensitivity for breast cancer detection. Gadobenate dimeglumine is a gadolinium-based contrast agent (GBCA) that is specifically approved in Europe for breast MRI and which has the highest r1 relaxivity among all GBCAs for this indication. In order to improve the diagnostic performance of breast MRI, several intra-individual crossover studies have evaluated gadobenate dimeglumine as a possible GBCA for this application. This review focuses on the role and advantages of gadobenate dimeglumine as a contrast agent for breast MRI by describing the unique properties of this agent and by summarizing published studies

Comparison of Magnetic Resonance Imaging and Serum Biomarkers for Detection of Human Pluripotent Stem Cell-Derived Teratomas.

The use of cells derived from pluripotent stem cells (PSCs) for regenerative therapies confers a considerable risk for neoplastic growth and teratoma formation. Preclinical and clinical assessment of such therapies will require suitable monitoring strategies to understand and mitigate these risks. Here we generated human-induced pluripotent stem cells (iPSCs), selected clones that continued to express reprogramming factors after differentiation into cardiomyocytes, and transplanted these cardiomyocytes into immunocompromised rat hearts post-myocardial infarction. We compared magnetic resonance imaging (MRI), cardiac ultrasound, and serum biomarkers for their ability to delineate teratoma formation and growth. MRI enabled the detection of teratomas with a volume >8 mm(3). A combination of three plasma biomarkers (CEA, AFP, and HCG) was able to detect teratomas with a volume >17 mm(3) and with a sensitivity of more than 87%. Based on our findings, a combination of serum biomarkers with MRI screening may offer the highest sensitivity for teratoma detection and tracking

A Comparative Study for 2D and 3D Computer-aided Diagnosis Methods for Solitary Pulmonary Nodules

Many computer-aided diagnosis (CAD) methods, including 2D and 3D approaches, have been proposed for solitary pulmonary nodules (SPNs). However, the detection and diagnosis of SPNs remain challenging in many clinical circumstances. One goal of this work is to investigate the relative diagnostic accuracy of 2D and 3D methods. An additional goal is to develop a two-stage approach that combines the simplicity of 2D and the accuracy of 3D methods. The experimental results show statistically significant differences between the diagnostic accuracy of 2D and 3D methods. The results also show that with a very minor drop in diagnostic performance the two-stage approach can significantly reduce the number of nodules needed to be processed by the 3D method, streamlining the computational demand