Contribution of organ blood flow, intrinsic tissue clearance and glycaemia to the regulation of glucose use in obese and type 2 diabetic rats: a PET study.

BACKGROUND AND AIMS: Chronic hyperglycaemia aggravates obesity and diabetes mellitus. The use of glucose by body organs depends on several factors. We sought to investigate the role of blood flow, intrinsic tissue glucose clearance and blood glucose levels in regulating tissue glucose uptake under fasting conditions (FCs) and in response to acute hyperglycaemia (AH) in obese and type 2 diabetic rats. METHODS AND RESULTS: Thirty-six Zucker rats were studied by positron emission tomography to quantify perfusion and glucose uptake during FC and after AH in the liver, myocardium, skeletal muscle and subcutaneous adipose tissue. Progressively higher glucose uptake rates were observed from lean to obese (p < 0.05) and to diabetic rats (p < 0.05) in all tissues during both FC and AH. In FC, they were increased of 7-18 times in obese rats and 11-30 times in diabetic rats versus controls. Tissue glucose uptake was increased by over 10-fold during AH in controls; this response was severely blunted in diseased groups. AH tended to stimulate organ perfusion in control rats. Tissue glucose uptake was a function of intrinsic clearance and glycaemia (mass action) in healthy animals, but the latter component was lost in diseased animals. Differences in perfusion did not account for those in glucose uptake. CONCLUSIONS: Each organ participates actively in the regulation of its glucose uptake, which is dependent on intrinsic tissue substrate extraction and extrinsic blood glucose delivery, but not on perfusion, and it is potently stimulated by AH. Obese and diabetic rats had an elevated organ glucose uptake but a blunted response to acute glucose intake.

Comparison of two dedicated 'in beam' PET systems via simultaneous imaging of (12)C-induced beta(+)-activity.

The selective energy deposition of hadrontherapy has led to a growing interest in quality assurance techniques such as 'in-beam' PET. Due to the current lack of commercial solutions, dedicated detectors need to be developed. In this paper, we compare the performances of two different 'in-beam' PET systems which were simultaneously operated during and after low energy carbon ion irradiation of PMMA phantoms at GSI Darmstadt. The results highlight advantages and drawbacks of a novel in-beam PET prototype against a long-term clinically operated tomograph for ion therapy monitoring.

An optimization-based method for geometrical calibration in cone-beam CT without dedicated phantoms.

In this paper we present a new method for the determination of geometrical misalignments in cone-beam CT scanners, from the analysis of the projection data of a generic object. No a priori knowledge of the object shape and positioning is required. We show that a cost function, which depends on the misalignment parameters, can be defined using the projection data and that such a cost function has a local minimum in correspondence to the actual parameters of the system. Hence, the calibration of the scanner can be carried out by minimizing the cost function using standard optimization techniques. The method is developed for a particular class of 3D object functions, for which the redundancy of the fan beam sinogram in the transaxial midplane can be extended to cone-beam projection data, even at wide cone angles. The method has an approximated validity for objects which do not belong to that class; in that case, a suitable subset of the projection data can be selected in order to compute the cost function. We show by numerical simulations that our method is capable to determine with high accuracy the most critical misalignment parameters of the scanner, i.e., the transversal shift and the skew of the detector. Additionally, the detector slant can be determined. Other parameters such as the detector tilt, the longitudinal shift and the error in the source-detector distance cannot be determined with our method, as the proposed cost function has a very weak dependence on them. However, due to the negligible influence of these latter parameters in the reconstructed image quality, they can be kept fixed at estimated values in both calibration and reconstruction processes without compromising the final result. A trade-off between computational cost and calibration accuracy must be considered when choosing the data subset used for the computation of the cost function. Results on real data of a mouse femur as obtained with a small animal micro-CT are shown as well, proving the capability of the proposed calibration method. In principle, the method can be adapted to other cone-beam imaging modalities (e.g., single photon emission computed tomography).

Experimental validation of the filtering approach for dose monitoring in proton therapy at low energy.

The higher physical selectivity of proton therapy demands higher accuracy in monitoring of the delivered dose, especially when the target volume is located next to critical organs and a fractionated therapy is applied. A method to verify a treatment plan and to ensure the high quality of the hadrontherapy is to use Positron Emission Tomography (PET), which takes advantage of the nuclear reactions between protons and nuclei in the tissue during irradiation producing beta(+)-emitting isotopes. Unfortunately, the PET image is not directly proportional to the delivered radiation dose distribution; this is the reason why, at the present time, the verification of depth dose profiles with PET techniques is limited to a comparison between the measured activity and the one predicted for the planned treatment by a Monte Carlo model. In this paper we test the feasibility of a different scheme, which permits to reconstruct the expected PET signal from the planned radiation dose distribution along beam direction in a simpler and more direct way. The considered filter model, based on the description of the PET image as a convolution of the dose distribution with a filter function, has already demonstrated its potential applicability to beam energies above 70 MeV. Our experimental investigation provides support to the possibility of extending the same approach to the lower energy range ([40, 70] MeV), in the perspective of its clinical application in eye proton therapy.

Fast 3D-EM reconstruction using Planograms for stationary planar positron emission mammography camera.

At the University of Pisa we are building a PEM prototype, the YAP-PEM camera, consisting of two opposite 6 x 6 x 3 cm3 detector heads of 30 x 30 YAP:Ce finger crystals, 2 x 2 x 30 mm3 each. The camera will be equipped with breast compressors. The acquisition will be stationary. Compared with a whole body PET scanner, a planar Positron Emission Mammography (PEM) camera allows a better, easier and more flexible positioning around the breast in the vicinity of the tumor: this increases the sensitivity and solid angle coverage, and reduces cost. To avoid software rejection of data during the reconstruction, resulting in a reduced sensitivity, we adopted a 3D-EM reconstruction which uses all of the collected Lines Of Response (LORs). This skips the PSF distortion given by data rebinning procedures and/or Fourier methods. The traditional 3D-EM reconstruction requires several times the computation of the LOR-voxel correlation matrix, or probability matrix {p(ij)}; therefore is highly time-consuming. We use the sparse and symmetry properties of the matrix {p(ij)} to perform fast 3D-EM reconstruction. Geometrically, a 3D grid of cubic voxels (FOV) is crossed by several divergent 3D line sets (LORs). The symmetries occur when tracing different LORs produces the same p(ij) value. Parallel LORs of different sets cross the FOV in the same way, and the repetition of p(ij) values depends on the ratio between the tube and voxel sizes. By optimizing this ratio, the occurrence of symmetries is increased. We identify a nucleus of symmetry of LORs: for each set of symmetrical LORs we choose just one LOR to be put in the nucleus, while the others lie outside. All of the possible p(ij) values are obtainable by tracking only the LORs of this nucleus. The coordinates of the voxels of all of the other LORs are given by means of simple translation rules. Before making the reconstruction, we trace the LORs of the nucleus to find the intersecting voxels, whose p(ij) values are computed and stored with their voxel coordinates on a hard disk. Only the non-zero p(ij) are considered and their computation is performed just once. During the reconstruction, the stored values are loaded and are available in the random access memory for all of the operations of normalization, backprojection and projection: these are now performed rapidly, because the application of the translation rules is much faster than the probability computations. We tested the algorithm on Monte Carlo data fully simulating the typical YAP-PEM clinical condition. The adopted algorithm gives an excellent positioning capability for hot spots in the camera FOV. To use all of the possible skew LORs in the FOV avoids the software rejection of collected data. Reconstructed images indicate that a 5mm diameter tumor of 37 kBq/cm3, in an active breast with a 10:1 Tissue to Background ratio (T/B), with a 10 min acquisition, for a head distance of 5 cm, can be detected by the YAP-PEM with a SNR of 8.7+/-1.0. The obtained SNR values depend linearly on the tumor volume. The algorithm allows one to discriminate between two hot sources of 5.0 mm diameter if they do not lie on the same axis. The YAP-PEM is now in the assembly stage.

Internet patient records: new techniques.

BACKGROUND: The ease by which the Internet is able to distribute information to geographically-distant users on a wide variety of computers makes it an obvious candidate for a technological solution for electronic patient record systems. Indeed, second-generation Internet technologies such as the ones described in this article--XML (eXtensible Markup Language), XSL (eXtensible Style Language), DOM (Document Object Model), CSS (Cascading Style Sheet), JavaScript, and JavaBeans--may significantly reduce the complexity of the development of distributed healthcare systems. OBJECTIVE: The demonstration of an experimental Electronic Patient Record (EPR) system built from those technologies that can support viewing of medical imaging exams and graphically-rich clinical reporting tools, while conforming to the newly emerging XML standard for digital documents. In particular, we aim to promote rapid prototyping of new reports by clinical specialists. METHODS: We have built a prototype EPR client, InfoDOM, that runs in both the popular web browsers. In this second version it receives each EPR as an XML record served via the secure SSL (Secure Socket Layer) protocol. JavaBean software components manipulate the XML to store it and then to transform it into a variety of useful clinical views. First a web page summary for the patient is produced. From that web page other JavaBeans can be launched. In particular, we have developed a medical imaging exam Viewer and a clinical Reporter bean parameterized appropriately for the particular patient and exam in question. Both present particular views of the XML data. The Viewer reads image sequences from a patient-specified network URL on a PACS (Picture Archiving and Communications System) server and presents them in a user-controllable animated sequence, while the Reporter provides a configurable anatomical map of the site of the pathology, from which individual "reportlets" can be launched. The specification of these reportlets is achieved using standard HTML forms and thus may conceivably be authored by clinical specialists. A generic JavaScript library has been written that allows the seamless incorporation of such contributions into the InfoDOM client. In conjunction with another JavaBean, that library renders graphically-enhanced reporting tools that read and write content to and from the XML data-structure, ready for resubmission to the EPR server. RESULTS: We demonstrate the InfoDOM experimental EPR system that is currently being adapted for test-bed use in three hospitals in Cagliari, Italy. For this we are working with specialists in neurology, radiology, and epilepsy. CONCLUSIONS: Early indications are that the rapid prototyping of reports afforded by our EPR system can assist communication between clinical specialists and our system developers. We are now experimenting with new technologies that may provide services to the kind of XML EPR client described here.