Sex-chromosome heterochromatin variation in the wood mouse, Apodemus sylvaticus.

Variation in heterochromatin content, as revealed by G- and C-banding, was studied in the sex chromosomes of the wood mouse, Apodemus sylvaticus. The sex-chromosome heterochromatin was also characterized by DAPI staining. Variation in sex chromatin was recorded in extremely large (giant) sex chromosomes in certain individuals and populations. In some individuals, the Y chromosome was the largest element of the complement. Different variants of both the X and Y chromosomes were found within a single population. The variation is therefore a type of population polymorphism and should not be used for taxonomic discrimination.

Effects of temporal modelling on the statistical uncertainty of spatiotemporal distributions estimated directly from dynamic SPECT projections.

Artefacts can result when reconstructing a dynamic image sequence from inconsistent single photon emission computed tomography (SPECT) projection data acquired by a slowly rotating gantry. The artefacts can lead to biases in kinetic parameters estimated from time-activity curves generated by overlaying volumes of interest on the images. Insufficient sampling and truncation of projections by cone-beam collimators can cause additional artefacts. To overcome these sources of bias in conventional image based dynamic data analysis, we have been investigating the estimation of time-activity curves and kinetic model parameters directly from dynamic SPECT projection data by modelling the spatial and temporal distribution of the radiopharmaceutical throughout the projected field of view. In the present work, we perform Monte Carlo simulations to study the effects of the temporal modelling on the statistical variability of the reconstructed spatiotemporal distributions. The simulations utilize fast methods for fully four-dimensional (4D) direct estimation of spatiotemporal distributions and their statistical uncertainties, using a spatial segmentation and temporal B-splines. The simulation results suggest that there is benefit in modelling higher orders of temporal spline continuity. In addition, the accuracy of the time modelling can be increased substantially without unduly increasing the statistical uncertainty, by using relatively fine initial time sampling to capture rapidly changing activity distributions.

Kinetic analysis of 125I-iodorotenone as a deposited myocardial flow tracer: comparison with 99mTc-sestamibi.

UNLABELLED: The goal of this investigation was to assess the accuracy of 7'-Z-[125I]iodorotenone (125I-iodorotenone) as a new deposited myocardial flow tracer and compare the results with those for 99mTc-sestamibi. METHODS: The kinetics of these two flow tracers were evaluated in 25 isolated, erythrocyte- and albumin-perfused rabbit hearts over a flow range relevant to patients. The two flow tracers and a vascular reference tracer (131I-albumin) were introduced simultaneously as a compact bolus through a port just above the aortic cannula in the absence of tracer recirculation. Myocardial extraction, retention, washout, and uptake parameters were computed from the venous outflow curves using the multiple-indicator dilution technique and spectral analysis. RESULTS: The extraction of 125I-iodorotenone was much higher than the extraction of 99mTc-sestamibi (0.84 +/- 0.05 vs. 0.48 +/- 0.10, respectively, P < 0.001). 125I-iodorotenone extraction was also less affected by flow than was 99mTc-sestamibi (P < 0.001). Net retention of 125I-iodorotenone was significantly greater than 99mTc-sestamibi net retention at 1 min (0.77 +/- 0.08 vs. 0.41 +/- 0.11, respectively, P < 0.001) and 26 min (0.46 +/- 0.13 vs. 0.27 +/- 0.11, respectively, P < 0.001) after tracer injection. Flow had less effect on 125I-iodorotenone net retention than on 99mTc-sestamibi net retention 1 min after tracer injection (P < 0.04). However, at 26 min, flow had an equivalent effect on the retention of both flow tracers (P < 0.4). The relationship between 125I-iodorotenone and 99mTc-sestamibi washout was complex and depended on elapsed time after isotope introduction and perfusion rate. Reflecting the favorable extraction and retention characteristics of 125I-iodorotenone, both its maximum myocardial uptake and its 26-min uptake were more closely related to flow than were those of 99mTc-sestamibi (P < 0.001 for both comparisons). CONCLUSION: The extraction and retention of 125I-iodorotenone were greater than those of 99mTc-sestamibi, making 125I-iodorotenone the superior flow tracer in the isolated rabbit heart.

Direct least-squares estimation of spatiotemporal distributions from dynamic SPECT projections using a spatial segmentation and temporal B-splines.

Artifacts can result when reconstructing a dynamic image sequence from inconsistent, as well as insufficient and truncated, cone beam single photon emission computed tomography (SPECT) projection data acquired by a slowly rotating gantry. The artifacts can lead to biases in kinetic model parameters estimated from time-activity curves generated by overlaying volumes of interest on the images. However, the biases in time-activity curve estimates and subsequent kinetic parameter estimates can be reduced significantly by first modeling the spatial and temporal distribution of the radiopharmaceutical throughout the projected field of view, and then estimating the time-activity curves directly from the projections. This approach is potentially useful for clinical SPECT studies involving slowly rotating gantries, particularly those using a single-detector system or body contouring orbits with a multidetector system. We have implemented computationally efficient methods for fully four-dimensional (4-D) direct estimation of spatiotemporal distributions from dynamic SPECT projection data. Temporal B-splines providing various orders of temporal continuity, as well as various time samplings, were used to model the time-activity curves for segmented blood pool and tissue volumes in simulated cone beam and parallel beam cardiac data acquisitions. Least-squares estimates of time-activity curves were obtained quickly using a workstation. Given faithful spatial modeling, accurate curve estimates were obtained using cubic, quadratic, or linear B-splines and a relatively rapid time sampling during initial tracer uptake. From these curves, kinetic parameters were estimated accurately for noiseless data and with some bias for noisy data. A preliminary study of spatial segmentation errors showed that spatial model mismatch adversely affected quantitative accuracy, but also resulted in structured errors (projected model versus raw data) that were easily detected in our simulations. This suggests iterative refinement of the spatial model to reduce structured errors as an area of future research.

List-mode maximum-likelihood reconstruction applied to positron emission mammography (PEM) with irregular sampling.

We present a preliminary study of list-mode likelihood reconstruction of images for a rectangular positron emission tomograph (PET) specifically designed to image the human breast. The prospective device consists of small arrays of scintillation crystals for which depth of interaction is estimated. Except in very rare instances, the number of annihilation events detected is expected to be far less than the number of distinguishable events. If one were to histogram the acquired data, most histogram bins would remain vacant. Therefore, it seems natural to investigate the efficacy of processing events one at a time rather than processing the data in histogram format. From a reconstruction perspective, the new tomograph presents a challenge in that the rectangular geometry leads to irregular radial and angular sampling, and the field of view extends completely to the detector faces. Simulations are presented that indicate that the proposed tomograph can detect 8-mm-diameter spherical tumors with a tumor-to-background tracer density ratio of 3:1 using realistic image acquisition parameters. Spherical tumors of 4-mm diameter are near the limit of detectability with the image acquisition parameters used. Expressions are presented to estimate the loss of image contrast due to Compton scattering.

Estimating glucose metabolism using glucose analogs and two tracer kinetic models in isolated rabbit heart.

The purpose of this investigation was to 1) evaluate the relative accuracy of the Sokoloff and Patlak tracer kinetic models in estimating glucose metabolic rate (GMR) in the presence and absence of insulin; 2) evaluate the effect of nutritional state on the lumped constant (LC); and 3) compare the kinetics of 2-fluoro-2-deoxy-D-[14C]glucose (FDG) and 2-deoxy-D-[3H]glucose (DG) membrane transport and phosphorylation. The experimental preparation was the isolated, red blood cell-albumin-perfused rabbit heart. Our results showed that both tracer kinetic models provided GMR estimates that correlated well with the Fick method (for FDG, R = 0. 84 and 0.91 for the Sokoloff and Patlak models, respectively); nutritional state did not affect the LC; and FDG and DG have different transport and/or phosphorylation parameters. We also observed that 1) the addition of a fourth compartment to the Sokoloff model reduced the mean squared error between measured and modeled data by a factor of 7.4; 2) a longer time (21.8 min) was required to obtain a linear phase of the Patlak plot than is allowed in clinical studies; and 3) accurate GMR estimates were obtained only by using different LCs reflecting insulin's presence or absence. Our results indicate potential sources of error in the use of FDG and positron emission tomography to quantify GMR in patients.

Kinetic parameter estimation from SPECT cone-beam projection measurements.

Kinetic parameters are commonly estimated from dynamically acquired nuclear medicine data by first reconstructing a dynamic sequence of images and subsequently fitting the parameters to time-activity curves generated from regions of interest overlaid upon the image sequence. Biased estimates can result from images reconstructed using inconsistent projections of a time-varying distribution of radiopharmaceutical acquired by a rotating SPECT system. If the SPECT data are acquired using cone-beam collimators wherein the gantry rotates so that the focal point of the collimators always remains in a plane, additional biases can arise from images reconstructed using insufficient, as well as truncated, projection samples. To overcome these problems we have investigated the estimation of kinetic parameters directly from SPECT cone-beam projection data by modelling the data acquisition process. To accomplish this it was necessary to parametrize the spatial and temporal distribution of the radiopharmaceutical within the SPECT field of view. In a simulated chest image volume, kinetic parameters were estimated for simple one-compartment models for four myocardial regions of interest. Myocardial uptake and washout parameters estimated by conventional analysis of noiseless simulated cone-beam data had biases ranging between 3-26% and 0-28%, respectively. Parameters estimated directly from the noiseless projection data were unbiased as expected, since the model used for fitting was faithful to the simulation. Statistical uncertainties of parameter estimates for 10,000,000 events ranged between 0.2-9% for the uptake parameters and between 0.3-6% for the washout parameters.

A methodology for specifying PET VOI's using multimodality techniques.

Volume-of-interest (VOI) extraction for radionuclide and anatomical measurements requires correct identification and delineation of the anatomical feature being studied. We have developed a toolset for specifying three-dimensional (3-D) VOI's on a multislice positron emission tomography (PET) dataset. The software is particularly suited for specifying cerebral cortex VOI's which represent a particular gyrus or deep brain structure. A registered 3-D magnetic resonance image (MRI) dataset is used to provide high-resolution anatomical information, both as oblique two-dimensional (2-D) sections and as volume renderings of a segmented cortical surface. VOI's are specified indirectly in two dimensions by drawing a stack of 2-D regions on the MRI data. The regions are tiled together to form closed triangular mesh surface models, which are subsequently transformed into the observation space of the PET scanner. Quantification by this method allows calculation of radionuclide activity in the VOI's, as well as their statistical uncertainties and correlations. The methodology for this type of analysis and validation results are presented.

Kinetic analysis of rubidium and thallium as deposited myocardial blood flow tracers in isolated rabbit heart.

Evaluation of myocardial perfusion with tracers such as thallium and rubidium is based on the assumption that tissue tracer content is proportional to flow. The purpose of this study was to evaluate the relationship between flow and tissue tracer content of 201Tl and 83Rb in the isolated perfused rabbit heart. 83Rb (86-day half-life), an isotope that is not used clinically, was used as a subsitute for 82Rb (76-s half-life) to improve the accuracy and precision of data acquisition. The multiple indicator-dilution technique was employed with two independent computational approaches. The first approach explicitly deconvolved 201Tl and 83Rb venous concentration curves by the intravascular reference tracer curve. The second approach used a conventional analysis. Both approaches showed that there was more early washout of 83Rb than 201Tl and that the heart retained 201Tl better than 83Rb within 2 min after isotope introduction. These data indicate that 201Tl is a better perfusion tracer than 83Rb in the isolated rabbit heart.

Strategies for extraction of quantitative data from volumetric dynamic cardiac positron emission tomography data.

The ability of positron emission tomography (PET) to serve as a useful myocardial perfusion indicator is well established. We describe a methodology for obtaining reliable quantitative kinetic parameters from dynamic cardiac PET data. Reconstructed images of the myocardium are subdivided into three-dimensional volumes of interest which are used to obtain quantitative measures of myocardial perfusion over physiologically meaningful anatomical regions. The quantitation technique rigorously models the uncertainty of estimated parameters while compensating for effects such as patient motion and partial volumes to arrive at model parameters with well-established confidence intervals.

High resolution EEG: 124-channel recording, spatial deblurring and MRI integration methods.

This paper describes a method for increasing the spatial detail of the EEG and for integrating physiological data with anatomical models based on magnetic resonance images (MRIs). This method includes techniques to efficiently record EEG data from up to 124 channels, to measure 3-D electrode positions for alignment with MRI-derived head models, and to estimate potentials near the outer convexity of the cortex using a spatial deblurring technique which uses a realistic model of the structure of the head and which makes no assumptions about the number or type of generator sources. The validity of this approach has been initially tested by comparing estimated cortical potentials with those measured with subdural grid recordings from two neurosurgical patients. The method is illustrated with somatosensory steady-state evoked potential data recorded from 5 healthy subjects. Results suggest that deblurred 124-channel topographic maps, registered with a subject's MRI and rendered in 3 dimensions, provide better spatial detail than has heretofore been obtained with scalp EEG recordings. The results also suggest that the potential for EEG as a functional neuroimaging modality has yet to be fully realized.

Seeing through the skull: advanced EEGs use MRIs to accurately measure cortical activity from the scalp.

There is a vast amount of untapped spatial information in scalp-recorded EEGs. Measuring this information requires use of many electrodes and application of spatial signal enhancing procedures to reduce blur distortion due to transmission through the skull and other tissues. Recordings with 124 electrodes are now routinely made, and spatial signal enhancing techniques have been developed. The most advanced of these techniques uses information from a subject's MRI to correct blur distortion, in effect providing a measure of the actual cortical potential distribution. Examples of these procedures are presented, including a validation from subdural recordings in an epileptic patient. Examples of equivalent dipole modeling of the somatosensory evoked potential are also presented in which two adjacent fingers are clearly separated. These results demonstrate that EEGs can provide images of superficial cortical electrical activity with spatial detail approaching that of O15 PET scans. Additionally, equivalent dipole modeling with EEGs appears to have the same degree of spatial resolution as that reported for MEGs. Considering that EEG technology costs ten to fifty times less than other brain imaging modalities, that it is completely harmless, and that recordings can be made in naturalistic settings for extended periods of time, a greater investment in advancing EEG technology seems very desirable.

Urinary excretion patterns of endogenously produced alcohols in type 1 (IDDM) and type 2 (NIDDM) diabetes mellitus compared with healthy control subjects.

Urinary excretion patterns of various endogenously produced alcohols, such as ethanol, propanol, isobutanol, butanol, and isopentanol, were evaluated in 17 type 1 (IDDM) and 15 type 2 (NIDDM) diabetic patients, and in two different groups of healthy control subjects (n = 12, n = 8, respectively) matched for sex, age and weight. In addition to the urinary alcohol excretion determined by gas-chromatography and mass-spectrometry, four cardiovascular reflex tests were performed, and the motor and sensory conduction velocities of three different peripheral nerves were measured. In the type 1 diabetic patients, urinary excretions of ethanol and propanol were significantly higher than in the control subjects (P less than 0.0001, P less than 0.00001, respectively), whereas the control subjects exhibited significantly higher urinary excretion rates of the other three alcohols (P less than 0.007, P less than 0.02 and P less than 0.002, respectively) compared with the type 1 diabetic patients. In the type 2 diabetic patients, only the urinary excretion of propanol was significantly elevated (P less than 0.002) compared with the control subjects, while the urinary excretion rates of butanol and isopentanol were significantly lower (P less than 0.02, P less than 0.05, respectively) than in the controls. Urinary alcohol excretions were not related to diabetic peripheral neuropathy in both groups studied. The clinical meaning of the urinary excretion patterns of different endogenously produced alcohols in diabetes mellitus has to be further evaluated.

Beyond topographic mapping: towards functional-anatomical imaging with 124-channel EEGs and 3-D MRIs.

A functional-anatomical brain scanner that has a temporal resolution of less than a hundred milliseconds is needed to measure the neural substrate of higher cognitive functions in healthy people and neurological and psychiatric patients. Electrophysiological techniques have the requisite temporal resolution but their potential spatial resolution has been not realized. Here we briefly review progress in increasing the spatial detail of scalp-recorded EEGs and in registering this functional information with anatomical models of a person's brain. We describe methods and systems for 124-channel EEGs and magnetic resonance image (MRI) modeling, and present first results of the integration of equivalent-dipole EEG models of somatosensory stimulation with 3-D MRI brain models.