Background: Cell permeable peptides (CPP) are a new class of carrier molecule to deliver biomolecules, radio-nucleotide and drugs that is gaining momentum. CPP are capable of entering into the cells by breaking the resistance of the membrane barrier and thus can be used universally in many cell types, which renders it an efficient carrier for both in-vitro and in-vivo use.
Methods: L-Maurocalcine (L-MCa), a peptide derived from scorpion venom was radiolabeled with 125I using the lactoperoxidase method. We achieved a specific activity of 45Mbq/nmole. In vitro studies with 125I-L-MCa in DAOY cells (human medulloblastoma) were studied in order to analyze the uptake of the peptide. 125I-L-MCa was injected intravenously in mice through tail vein and bio-distribution was studied using single photon emission tomography/computed tomography (SPECT/CT).
Results: The cellular uptake of the 125I-L-MCa in DAOY cells was time and dose dependent suggesting that the radiolabeled peptide retains the biological property after radiolabeling. We have observed no loss of cell viability upon uptake of 125I-L-MCa, favoring that this peptide has potential for use in in vivo studies. The distribution of the 125I-L-MCa in mice revealed its uptake in the liver, kidney and stomach. Interestingly the 125I-L-MCa was cleared from the circulation 24h post injection, thus providing another advantage for its use in in vivo studies.
Conclusions: In the present study we have shown the uptake of 125I-L-MCa in DAOY cells. Further, the 125I-L-MCa when injected in mice localized to the liver, kidney and stomach as revealed by SPECT/CT. Cells labeled with 125I-L-MCa can possibly be tracked to their target site.
Accurate diagnosis of tumor type is vital for effective treatment planning. Diagnosis relies heavily on tumor biopsies and other clinical factors. However, biopsies do not fully capture the tumor’s heterogeneity due to sampling bias and are only performed if the tumor is accessible. An alternative approach is to use features derived from routine diagnostic imaging such as magnetic resonance (MR) imaging. In this study we aim to establish the use of quantitative image features to classify brain tumors and extend the use of MR images beyond tumor detection and localization. To control for interscanner, acquisition and reconstruction protocol variations, the established workflow was performed in a preclinical model. Using glioma (U87 and GL261) and medulloblastoma (Daoy) models, T1-weighted post contrast scans were acquired at different time points post-implant. The tumor regions at the center, middle, and peripheral were analyzed using in-house software to extract 32 different image features consisting of first and second order features. The extracted features were used to construct a decision tree, which could predict tumor type with 10-fold cross-validation. Results from the final classification model demonstrated that middle tumor region had the highest overall accuracy at 79%, while the AUC accuracy was over 90% for GL261 and U87 tumors. Our analysis further identified image features that were unique to certain tumor region, although GL261 tumors were more homogenous with no significant differences between the central and peripheral tumor regions. In conclusion our study shows that texture features derived from MR scans can be used to classify tumor type with high success rates. Furthermore, the algorithm we have developed can be implemented with any imaging datasets and may be applicable to multiple tumor types to determine diagnosis.
The basic VRX technique boosts spatial resolution of a CT scanner in the scan plane by two or more orders of magnitude by reducing the angle of incidence of the x-ray beam with respect to the detector surface. A four-arm Variable-Resolution X-ray (VRX) detector has been developed for CT scanning. The detector allows for "target imaging" in which an area of interest is scanned at higher resolution than the remainder of the subject, yielding even higher resolution for the focal area than that obtained from the basic VRX technique. The new VRX-CT detector comprises four quasi-identical arms each containing six 24-cell modules (576 cells total). The modules are made of individual custom CdWO4 scintillators optically-coupled to custom photodiode arrays. The maximum scan field is 40 cm for a magnification of 1.4. A significant advantage of the four-arm geometry is that it can transform quickly to the two-arm, or even the single-arm geometry, for comparison studies. These simpler geometries have already been shown experimentally to yield in-plane CT detector resolution exceeding 60 cy/mm (<8μ) for small fields of view. Geometrical size and resolution limits of the target VRX field are calculated. Two-arm VRX-CT data are used to simulate and establish the feasibility of VRX CT target imaging. A prototype target VRX-CT scanner has been built and is undergoing initial testing.
The Variable Resolution X-ray (VRX) CT system, developed at the UTHSC, Memphis, has the potential for use in animal imaging. Animal models of tumor progression and pharmacological impact are becoming increasingly important in understanding the molecular and mechanistic basis of tumor development. In general, CT-imaging offers several advantages in animal research: a fast throughput of seconds to minutes reducing the physiological stress animals are exposed to, and it is an inexpensive modality affordable to many animal laboratories. We are developing the VRX CT scanner as a non-invasive imaging modality to measure tumor volume, progression, and metastasis. From the axial images taken by the VRX CT-scanner, tumor area was measured and the tumor volume was calculated. Animals were also imaged using an optical liquid nitrogen-cooled CCD camera to detect tumor fluorescence. A simple image fusion with a planner x-ray image was used to ascertain the position of the tumors, animals were then sacrificed the tumors excised, and the tumor volume calculated by physical measurements. Furthermore, using a specially designed phantom with three spheres of different volumes, we demonstrated that our system allowed us to estimate the volume with up to 10% accuracy; we expect this to increase dramatically in the next few months.
In this paper, we report our investigation using a CsI(Tl) transparent scintillator x-ray detector together with the multi-level scheme algebraic reconstruction technique (MLS- ART) for megavoltage computed tomography (CT) reconstructions. The reconstructed CT images may be useful for positional verification in radiotherapy. The CsI(Tl) imaging system consists of a scintillator screen coupled to a liquid- nitrogen-cooled slow-scan CCD-TV camera. This system provides better contrast resolution than the standard electronic portal imaging system (EPID), which is especially useful given the low number of projections we are aiming at. The geometry of the imaging system has also been optimized to achieve high spatial resolution (1 lp/mm) in spite of the thickness of the screen. We present the images reconstructed using a pediatric head phantom using a total of 99 projections, and a combined phantom using 50 projections. Image reconstruction was carried out using the MLS-ART technique. We also present the CT images obtained using the back projection technique for comparison purposes.
We investigate the use of the kinestatic charge detector (KCD) together with the multi-level scheme algebraic reconstruction technique (MLS-ART) for computer tomography (CT) reconstruction, to be used in position verification in radiotherapy. The KCD offers very good contrast resolution, which is especially useful given the low number of projections we are aiming at. We present the images reconstructed using a head phantom (Rando-phantom) using a total of 95 projections, and a standard low contrast CT phantom using 63 projections. The reconstruction was carried out using MLS-ART technique, in this technique satisfactory images are generally obtained after one or two iteration, which in effect makes ART a noniterative algorithm. We also present the CT images obtained using the back projection technique for comparison purposes.
Frank DiBianca, Carlos Rodriguez, Sreenivas Devidas, Donald Emerson, M. Waleed Gaber, George Giakos, Robert Gold, Lawrence Jordan, Robert Kaufman, Shashidhar Kollipara, Joseph Laughter, Azad Mahmud, Senthilkumar Nagarajan, Qian Peng, Pamela Price, Jeno Sebes, Herbert Zeman, Zeping Zhu
The initial clinical performance of a research prototype digital radiographic system based on a large-field (2016-channel) kinestatic charge detector and data acquisition system is discussed. The first clinical images from the large-field system are compared with images of the same patients taken with commercial systems. Future directions are discussed.
Kinestatic charge detector (KCD) systems have potential uses in all fields of digital radiography including chest, abdominal, vascular, peripheral, dual energy subtraction and mammography. The purpose of this study was to investigate the development of a chest imaging protocol for a full field of view KCD system with regard to the effect of significant variations in patient chest thickness and its possible influence on kinestatic electric field settings. This was investigated by optimizing the kinestatic setting for a 5 lp/mm bar pattern imaged with 0, 5, 10, 15, and 20 cm of added Lucite to simulate varying patient chest thickness. Preliminary results demonstrate that variation in kinestatic settings due to variations in patient thickness affects the kinestatic electric field setting. Since only one field setting is available per image scan it becomes necessary to either optimize kinestatic settings for an estimated average patient thickness or for the density function of the expected region of interest (ROI).
A kinestatic charge detector (KCD) with fourteen segmented signal collectors was built to evaluate the imaging performance of the single-scan dual energy x-ray KCD system. Those front segments of the KCD collectors will produce a low energy signal and those rear segments will produce a high energy signal. The middle segments between the front and rear work as an inactive filter to increase the separation of mean energies absorbed in the front and rear segments. In this study, the segmented KCD output signals were measured and compared with the Monte Carlo simulated result. An optimal KCD collector configuration is gotten by mapping the low energy and high energy signal amplitude to the predetermined thickness of the lucite-aluminum wedge-phantom (0-228.6 mm lucite and 0-25.4 mm aluminum), and then performing error analysis between the calculated thickness and known thickness.
The kinestatic charge detector (KCD) built and researched at the University of Tennessee, Memphis, is now being studied as a possible dual-energy x-ray imager. The present study aims at quantifying the change in the arrival time spectrum (ATS) as a function of the detector's depth, i.e., in the x-ray direction. We measured the change in the full width at half maximum (FWHM) along the x-ray direction in the chamber using a segmented signal- collector board. The FWHM of the ionic signal exhibit a dependence on the x-ray beam intensity, and electric field strength. Furthermore, the average arrival time is almost constant along the detector depth.
Experimental studies of the broadening of the full width at half maximum (FWHM) of the arrival time spectrum (ATS) in the research KCD system as a function of drift distance and x- ray tube mA settings were carried out. Results demonstrate that the broadening of the FWHM is mainly due to two factors, the space charge spreading of the ionic plane and the presence of more than one charge carrier with different mobilities in the ionic plane. Diffusional broadening is estimated to be almost negligible.
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