Dopaminergic manipulations and its effects on neurogenesis and motor function in a transgenic mouse model of Huntington's disease.

Huntington's disease (HD) is an inherited neurodegenerative disorder that is classically defined by a triad of movement and cognitive and psychiatric abnormalities with a well-established pathology that affects the dopaminergic systems of the brain. This has classically been described in terms of an early loss of dopamine D2 receptors (D2R), although interestingly the treatments most effectively used to treat patients with HD block these same receptors. We therefore sought to examine the dopaminergic system in HD not only in terms of striatal function but also at extrastriatal sites especially the hippocampus, given that transgenic (Tg) mice also exhibit deficits in hippocampal-dependent cognitive tests and a reduction in adult hippocampal neurogenesis. We showed that there was an early reduction of D2R in both the striatum and dentate gyrus (DG) of the hippocampus in the R6/1 transgenic HD mouse ahead of any overt motor signs and before striatal neuronal loss. Despite downregulation of D2Rs in these sites, further reduction of the dopaminergic input to these sites by either medial forebrain bundle lesions or receptor blockade using sulpiride was able to improve both deficits in motor performance and adult hippocampal neurogenesis. In contrast, a reduction in dopaminergic innervation of the neurogenic niches resulted in impaired neurogenesis in healthy WT mice. This study therefore provides evidence that D2R blockade improves hippocampal and striatal deficits in HD mice although the underlying mechanism for this is unclear, and suggests that agents working within this network may have greater effects than previously thought.

Ultra fast symmetry and SIMD-based projection-backprojection (SSP) algorithm for 3-D PET image reconstruction.

Remarkable progress in positron emission tomography (PET) development has occurred in recent years, in hardware, software, and computer implementation of image reconstruction. Recent development in PET scanners such as the high-resolution research tomograph (HRRT) developed by CTI (now Siemens) represents such a case and is capable of greatly enhanced resolution as well as sensitivity. In these PET scanners, the amount of coincidence line data collected contains more than 4.5 x 10(9) coincidence lines of response generated by as many nuclear detectors as 120 000. This formidable amount of data and the reconstruction of this data set pose a real problem in HRRT and have also been of the major bottle neck in further developments of high resolution PET scanners as well as their applications. In these classes of PET scanners, therefore, obtaining one set of reconstructed images often requires many hours of image reconstruction. For example, in HRRT with full data collection in a normal brain scan (using SPAN 3), the image reconstruction time is close to 80 min, making it practically impossible to attempt any list-mode-based dynamic imaging since the image reconstruction time would take many days (as much as 43 h or more for 32-frame dynamic image reconstruction). To remedy this data-handling problem in image reconstruction, we developed a new algorithm based on the symmetry properties of the projection and backprojection processes, especially in the 3-D OSEM algorithm where multiples of projection and back-projection are required. In addition, the single-instruction multiple-data (SIMD) technique also allowed us to successfully incorporate the symmetry properties mentioned above, thereby effectively reducing the total image reconstruction time to a few minutes. We refer to this technique as the symmetry and SIMD-based projection-backprojection (SSP) technique or algorithm and the details of the technique will be discussed and an example of the application of the technique to the HRRT's OSEM algorithm will be presented as a demonstration.

The effect of Ting point (tendinomuscular meridians) electroacupuncture on thermal pain: a model for studying the neuronal mechanism of acupuncture analgesia.

OBJECTIVE: The aim of this study was to characterize the role of Ting points (TP) in acute pain management and its potential use in functional imaging studies by quantitatively assessing: (1) the change in peripheral thermal thresholds before and after the electroacupuncture (EA); and (2) the corresponding behavioral feedback of thermal pain stimulation and the de qi sensation of EA. DESIGN: The study design was prospective. SETTINGS/LOCATION: Healthy subjects were recruited for the study at the University of California, San Diego Medical Center. SUBJECTS/INTERVENTIONS: Thirteen (13) healthy subjects were studied. Baseline thermal thresholds (cold and warm sensations and cold and hot pain) were measured at premarked testing sites along the medial aspects of bilateral lower extremities. Five (5) seconds of hot pain (HP) was delivered to the testing sites and the corresponding pain visual analog scale (VAS) scores were recorded. Thirty (30) seconds of EA was delivered via the SP1 and LR1 on the left lower extremities at 5 Hz via a 6-V square-wave stimulator. OUTCOME MEASURES: The VAS scores of the HP and de qi sensation (tingling) during the EA were recorded. The thermal thresholds and VAS scores for the HP and de qi were obtained immediately and both 30 and 60 minutes after the EA. Adaptation testing was also carried out to assess the change in thermal thresholds and the VAS scores of HP without EA. RESULTS: The warm thresholds of bilateral medial calves significantly increased (p < 0.01) after 30 seconds of EA stimulation. The HP VAS score reduced significantly at the ipsilateral calf during EA in comparison to preacupuncture and postacupuncture (p < 0.01) measurements. No significant change in thermal thresholds was noted in the adaptation paradigm. CONCLUSIONS: EA at the TP has an inhibitory effect on the C-fiber afferents. The analgesic benefit observed is most likely A-delta afferent mediated. Further correlation studies in functional imaging may provide defining data for the observed analgesic mechanism.

Semiconductor camera for detection of small tumors.

Early detection of small tumors (approximately 3 mm) with only a moderate uptake ratio is often difficult because of poor statistics and a small signal-to-background ratio. The detection capability of a germanium semiconductor camera is analyzed to show that a very large number of counts is required even when the spatial resolution is matched to the size of the tumor. A potential enhancement of statistics using the tissue-scattered gamma rays is discussed based on the superior energy resolution of the semiconductor.

Bismuth germanate as a potential scintillation detector in positron cameras.

Timing and energy resolutions of the bismuth germanate (Bi4Ge3O12) scintillation crystals were studied, with particular respect to a positron-camera application. In comparison with the NaI(Tl) system, the detection efficiency for annihilation radiation is more than triple, and coincidence detection efficiency is more than ten times as good. This paper explores the properties of the new scintillator material and their bearing on the spatial resolution and the efficiency of coincidence detection in positron cameras with stationary ring detectors.

Wedge-shaped BGO scintillation crystal for positron emission tomography: concise communication.

In order to increase the detection efficiency and also reduce the interdetector spillage, a new wedge-shaped BGO scintillation detector array is proposed. By shaping the front part of a detector as a wedge, the absorption path becomes longer, particularly for obliquely incident photons, thereby improving the uniformity in the sensitivity for the incident photons of different angles. To demonstrate the effectiveness of the proposed detector shape, a Monte Carlo simulation was performed and the results are presented.

Positron ranges obtained from biomedically important positron-emitting radionuclides.

Positron ranges were obtained experimentally for several nuclides used in scintigraphic imaging. The nuclides examined were 13C, 13N, 15O, 18F, 68Ga, and 82Rb. The results are discussed with respect to the ultimate spatial resolution obrained in a scintigraphic image.

Nuclear magnetic resonance microscopic ocular imaging for the detection of early-stage cataract.

A nuclear magnetic resonance (NMR) microscopic ocular imaging was performed at 7.0 Tesla to investigate its usefulness in the detection of early-stage cataracts. For this study, galactose cataracts were generated in experimental rabbits through diet (35% galactose), and enucleated eyes were imaged at various times after initiation of the diet. In previous studies using a 0.6 Tesla conventional magnetic resonance imager (MRI), the contrast between normal and cataractous tissues in the lens was not well defined, mainly due to the partial volume effect coming from the limitation of resolution and signal-to-noise ratio (SNR). With resolution of 60 X 60 X 80 microns, early localized precataractous tissue changes were clearly observed after 5 days diet. Precataractous tissue changes were seen histologically but no visible evidence of lens change was detected by the conventional slit lamp biomicroscope at this time. Substantially elongated spin-spin relaxation times (T2) in localized cataractous tissues (72.4 +/- 8.8 msec) were consistently observed compared with those in normal lens region (16.1 +/- 3.2 msec); however, the changes of the spin-lattice relaxation time (T1) were not significant. Some ocular NMR microscopic images with corresponding histological photographs are demonstrated to show the potential of NMR microscopy.

Localized in vivo high-resolution NMR imaging using gradient subencoding technique.

A new spatial localization technique for in vivo high-resolution imaging is presented here. In contrast to other localization techniques that use a series of rf pulses to define a volume of interest, only one rf pulse is utilized in the proposed method for selection of a region to be imaged. Instead of rf pulses for region selection, subencoding gradient pulses are used for the localization together with a convolution process on each phase-encoding gradient by a set of additional gradients (e.g., y direction). Then the 2-D localization is completed by restricting the bandwidth in the readout direction (e.g., x direction). The latter is simply achieved by using a low-pass filter in the receiver system. By applying this technique on a human body, localized in vivo high-resolution images are obtained for the knee with much improved resolution. 100 x 100 microns in-plane (x,y plane) resolution images obtained from the human knee demonstrate that localized in vivo high-resolution imaging for both human and animals is possible with an in-plane resolution of below 100 microns.

A generalized formulation of diffusion effects in micron resolution nuclear magnetic resonance imaging.

A generalized formulation of the diffusion related nuclear magnetic resonance (NMR) signal is derived from a random walk model. Previous analyses performed in the NMR spectroscopy were the formulations of the diffusion related signal amplitude at a specific time, such as the spin echo formation time. They are, in general, not applicable to continuous time domain analyses. In this paper, we have extended the theory to the two-dimensional imaging case and derived an analytical formula useful for the computation of the diffusion affected signal as a function of continuous time for a time variant gradient. This formulation will be useful in NMR imaging, especially in NMR microscopy where the diffusion associated signal attenuation is serious due to the strong gradient fields (100-1000 G/cm), and at the same time data are acquired continuously for the acquisition period. In addition to the loss of the resolution and signal-to-noise ratio due to the random phase fluctuation by diffusion, the variation of the intensity during the data acquisition period introduces a line broadening whose full width at half-maximum is found to be much larger than the bandwidth-limited resolution or diffusion related intrinsic resolution. This line spreading effect is integrated in a computer simulation and is evaluated as an integral part of the overall diffusion effects in micron resolution NMR imaging or NMR microscopy.

Total inhomogeneity correction including chemical shifts and susceptibility by view angle tilting.

A correction technique of the total magnetic field inhomogeneity effects including the localized object induced inhomogeneities such as chemical shift and susceptibility is developed and its usefulness is experimentally demonstrated. With this new and simple technique all the inhomogeneity induced artifacts can be corrected simultaneously. The basic idea of this method is to add a compensation gradient of the same amplitude as the selection gradient in simultaneity with the reading gradient in such a way that the view angle is tilted. Thereby all the inhomogeneity induced geometrical shifts and hence the intensity changes are corrected, since the addition of the compensation which is independent from the field inhomogeneities including both chemical shifts and susceptibility. This technique has been theoretically examined and its usefulness is demonstrated by experiments.

The effects of random directional distributed flow in nuclear magnetic resonance imaging.

Capillary flow or microscopic random directional coherent flow as a model of perfusion is investigated both theoretically and experimentally. In the model, we assumed that molecular motion within a finite resolvable volume element (voxel) is a superposition of flow of randomly oriented small capillaries. In such a case, the observed signal from the capillary flow within a voxel will be attenuated in signal amplitude without any change in phase. Although this attenuation effect is similar to the diffusion phenomenon, it differs basically in the following aspects: since the motion in each capillary segment is coherent, phase cancellation occurs at even echoes due to spin rephasing, while the diffusion phenomenon is a purely random Brownian motion of the thermally agitated molecules, changing both in direction and speed during the measurement period. Because of the random character of diffusion, even-echo rephasing cannot be observed. Thus capillary flow or perfusionlike microscopic flow can be measured based on the above distinct flow characteristics, i.e., signal restoration at even echoes versus signal amplitude attenuation at odd echoes. By applying a suitable mathematical algorithm, information on the capillary flow alone can be extracted from the two separate distinct measurements, i.e., one with a single echo and the other with a double echo. Both a theoretical calculation of the capillary flow, as well as the experimental results with a human volunteer by a 0.6-T nuclear magnetic resonance imager, are presented.

An improved nuclear magnetic resonance diffusion coefficient imaging method using an optimized pulse sequence.

Two-dimensional diffusion coefficient maps (images) of a carefully controlled diffusion phantom have been measured by a new diffusion imaging sequence using a 0.6-T whole-body nuclear magnetic resonance (NMR) scanner having a gradient field strength of 2.5 mT/m. The free induction decay (FID) data for the diffusion coefficient images were collected by varying the duration of the readout gradient in the conventional two-dimensional Fourier imaging sequence. The experimental results obtained by the proposed NMR diffusion measurement technique indicate a close agreement with other previous measurements. The selection of optimum spin-echo time for maximum signal-to-noise ratio (SNR) in diffusion imaging is studied and also experimentally confirmed. Finally, a preclinical study with human volunteers has been performed and results are presented.

Nuclear magnetic resonance microscopy with 4-microns resolution: theoretical study and experimental results.

Nuclear magnetic resonance (NMR) microscopy with 4-microns resolution, a step closer to the 1-micron resolution with which in vivo cellular imaging would be possible is described. An analysis of the ultimate resolution and voxel size dependent signal-to-noise ratio (SNR) in NMR microscopy is presented and experimentally verified. For microscopic scale objects (less than 1-mm diameter), the SNR based on the geometrical scale factor(s) is found to be proportional to sn where n less than 2, rather than n = 3 as previously supposed. This comes about because of a drastic reduction in sample noise coupled with a significant sensitivity gain realized in small diameter radiofrequency coils. A new pulse sequence which reduces both diffusion dependent resolution degradation and signal attenuation is presented. The selection of optimal bandwidth and acquisition time for maximal SNR is discussed. Experimental results obtained on both a 2.0-T whole-body system and a 7.0-T small bore system adapted for microscopy indicate the potentials of 4-microns resolution microscopy with the existing magnets.

A new phase correction method in NMR imaging based on autocorrelation and histogram analysis.

A new statistical approach to phase correction in NMR imaging is proposed. The proposed scheme consists of first-and zero-order phase corrections each by the inverse multiplication of estimated phase error. The first-order error is estimated by the phase of autocorrelation calculated from the complex valued phase distorted image while the zero-order correction factor is extracted from the histogram of phase distribution of the first-order corrected image. Since all the correction procedures are performed on the spatial domain after completion of data acquisition, no prior adjustments or additional measurements are required. The algorithm can be applicable to most of the phase-involved NMR imaging techniques including inversion recovery imaging, quadrature modulated imaging, spectroscopic imaging, and flow imaging, etc. Some experimental results with inversion recovery imaging as well as quadrature spectroscopic imaging are shown to demonstrate the usefulness of the algorithm.

Measurement of bulk and random directional velocity fields by NMR imaging.

A formalism for the multidimensional measurement of velocity fields in liquids by nuclear magnetic resonance (NMR) is introduced. We assume that the velocity at any point within a flow field is given by a superposition of two velocity components. The first one is taken to represent the mean bulk velocity within a voxel and the second component is assumed to be random directional such as one may find in the capillary beds or porous materials. We show that the random directional flow leads to an extra dephasing of the nuclear magnetization in addition to molecular diffusion and spin-spin relaxation (T2) processes. The coherent bulk flow introduces a phase distortion in the NMR images. A procedure for measuring the spin density as well as the two velocity fields is described.

Analysis of the eddy-current induced artifacts and the temporal compensation in nuclear magnetic resonance imaging.

Reduction of eddy currents by a temporal compensation of the input current waveform to the gradient coil is studied with an analytic solution. The technique is the inverse filtering of the eddy-current affected field response, which is calculated from the diffusion equation. The limitation of the temporal compensation due to the spatially variant eddy currents is also investigated for whole-body diagnostic imaging systems and small-bore nuclear magnetic resonance (NMR) microscopy systems. Within a limited imaging volume of less than 60% of the gradient coil diameter, most of eddy-current problems can be solved by the technique.

Incremental algorithm-a new fast backprojection scheme for parallel beam geometries.

A fast backprojection scheme for parallel beam geometries is proposed. Known as the incremental algorithm, it performs backprojection on a ray-by-ray (beam-by-beam) basis rather than the pixel-by-pixel backprojection in the conventional algorithm. By restructuring a conventional backprojection algorithm, the interdependency of pixel computations (position and value) is transformed to a set of incremental relations for a beam, where a beam is a set of pixels enclosed by two adjacent rays in 2-D computed tomography (CT), and a set of voxels enclosed by four adjacent rays in 3-D CT. To minimize the overhead of searching for the next pixels, a searching flow technique has been developed to implement the first-order and second-order incremental relations for 2-D and 3-D CTs, respectively. The values of all the pixels in each beam (except the first pixel) are computed with additions only, the key idea of the proposed backprojection scheme. The incremental algorithm has been implemented on two different machines and compared to B.F. Shepp and L.A. Logan's (1974) algorithm. The present implementation results show the superiority of this approach over the conventional algorithm.

Parallelization of the EM algorithm for 3-D PET image reconstruction.

The EM algorithm for PET image reconstruction has two major drawbacks that have impeded the routine use of the EM algorithm: the long computation time due to slow convergence and a large memory required for the image, projection, and probability matrix. An attempt is made to solve these two problems by parallelizing the EM algorithm on multiprocessor systems. An efficient data and task partitioning scheme, called partition-by-box, based on the message passing model is proposed. The partition-by-box scheme and its modified version have been implemented on a message passing system, Intel iPSC/2, and a shared memory system, BBN Butterfly GP1000. The implementation results show that, for the partition-by-box scheme, a message passing system of complete binary tree interconnection with fixed connectivity of three at each node can have similar performance to that with the hypercube topology, which has a connectivity of log(2) N for N PEs. It is shown that the EM algorithm can be efficiently parallelized using the (modified) partition-by-box scheme with the message passing model.