Biomedical subjects

Su Xu

Publications and source records attributed to Su Xu.

8 recordsLinked to original sources

PubMed2004

Thermal and conformational stability of Ssh10b protein from archaeon Sulfolobus shibattae.

The secondary structure of the DNA binding protein Ssh10b is largely unaffected by change in temperature between 25 degrees C and 85 degrees C, indicating that the protein is highly thermostable. Here, we report the temperature-dependent equilibrium denaturation of Ssh10b in the presence of guanidine hydrochloride (GdnHCl). It was found that the transition midpoint values of the temperature (T(m)), and changes of enthalpy (DeltaH(m)) and entropy (DeltaS(m)) of Ssh10b unfolding were linearly decreasing with increasing GdnHCl concentration. The true values of the thermodynamic parameters, T(m)=402 K, DeltaH(m)=590+/-40 kJ x mol(-1) and DeltaS(m)=1.4+/-0.15 kJ x T(-1) x mol(-1), were obtained by linear extrapolation to 0 M GdnHCl. The value of the heat capacity change of Ssh10b unfolding, DeltaC(p)=3.8+/-0.2 kJ x T(-1) x mol(-1) (approx. 19 J T(-1) x mol residue(-1)), was obtained from the measured thermodynamic parameters. This is significantly smaller than that of the average value for mesophilic proteins (50 J.K(-1) x mol residue(-1)) or the value calculated from the Ssh10b structural data (64 J T(-1) x mol residue(-1)). A consequence of the small DeltaC(p) is that the DeltaG of Ssh10b is larger than that of mesophilic proteins, while the values of DeltaH and T*DeltaS are smaller. The small DeltaC(p) of Ssh10b appears to result mainly from the presence of compactness in the denatured state.

Archaeal Proteins↗

PubMed2003

Circular spectrum mapping for intravoxel fiber structures based on high angular resolution apparent diffusion coefficients.

A method is presented for mapping intravoxel fiber structures using spectral decomposition onto a circular distribution of measured apparent diffusion coefficients (ADCs). The zeroth-, second-, and fourth-order harmonic components of the ADC distribution on the circle spanned by the major and median eigenvectors of the diffusion tensor can be used to provide quantitative indices for isotropic, linear, and fiber-crossing diffusion, respectively. A diffusion-weighted MRI technique with 90 encoding orientations was implemented to estimate the circular ADC distribution and calculate the circular spectrum. A digital phantom was used to simulate various diffusion patterns. Comparisons were made between the circular spectrum and regular DTI-based index maps. The results indicated that the zeroth- and second-order circular spectrum maps exhibited a strong consistency with the DTI-based mean diffusivity and linear indices, respectively, and the fourth-order circular spectrum map was able to identify the fiber crossings. MRI experiments were performed on seven healthy human brains using a 3T scanner. The in vivo fourth-order maps showed significantly higher densities in several brain regions, including the corpus callosum, cingulum bundle, superior longitudinal fasciculus, corticospinal tract, and middle cerebellar peduncle, which indicated the existence of fiber crossings in these regions.

Adult↗

PubMed2003

Detection and quantitative analysis of early stage orthotopic murine bladder tumor using in vivo magnetic resonance imaging.

PURPOSE: We evaluated in vivo magnetic resonance imaging (MRI) as a noninvasive method for early detection and quantitative measurements of superficial tumors in an orthotopic murine bladder tumor model. MATERIALS AND METHODS: Murine bladder tumor cells were instilled into 25 mouse bladders and subsequently scanned with MRI 10, 14, 17 and 24 days after tumor inoculation. High quality T1-weighted spin-echo transverse images were obtained with 1.5 mm thick slices. Conditions for contrast agent instillation were optimized by evaluating varying concentrations of Gd-diethylenetetramine pentaacetic acid, water and air. Total tumor area in the largest bladder section on MRI was measured and compared quantitatively with actual tumor areas measured in whole mount bladder step sections. RESULTS: Optimal MRI studies were obtained with intravesical instillation of 50 microl Gd-diethylenetetramine pentaacetic acid and 50 microl air. Overall 17 tumors in 11 mice were identified pathologically 10 days after tumor inoculation, of which 14 (82.4%) were identified by MRI with a largest mean diameter of 1.4 +/- 0.1 mm (range 1.0 to 2.2). Mean total tumor area on MRI 10, 14, 17 and 24 days after tumor inoculation was 0.024 +/- 0.005, 0.108 +/- 0.049, 0.165 +/- 0.020 and 0.318 +/- 0.023 cm2, respectively, which correlated well with actual tumor area (r2 = 0.977, p <0.001). CONCLUSIONS: MRI is accurate and effective for noninvasively monitoring tumor growth in the orthotopic murine bladder cancer model. The improved resolution that we report compared with previous murine bladder studies highlights its potential for monitoring the therapeutic efficacy of antitumor agents for early superficial bladder tumors.

Animals↗

PubMed2003

Murine S factors for liver, spleen, and kidney.

UNLABELLED: Preclinical evaluation of new radiopharmaceuticals is performed in animal systems before testing is started in humans. These studies, often performed in murine or other rodent models, are important in understanding the relationship between absorbed dose and response, which can be translated to preclinical results for humans. In performing such calculations, either electrons are assumed to deposit all of their energy locally or idealized models of mouse anatomy are used to determine absorbed fractions. Photon contributions are generally considered negligible. To improve the accuracy of such absorbed dose calculations, mouse-specific S factors for (131)I, (153)Sm, (32)P, (188)Re, and (90)Y have been generated, and the photon and electron portions have been tabulated separately. Absorbed fractions for 5 monoenergetic electrons, ranging in energy from 0.5 to 2 MeV, are also provided. METHODS: Female athymic mouse MR images were obtained on a 4.7-T MRI device. Fifteen T1-weighted, 1.5-mm-thick slices (0.5-mm gap) were collected. Using a previously developed software package, 3-dimensional Internal Dosimetry (3D-ID), organ contours were drawn to obtain a 3-dimensional representation of liver, kidneys, and spleen. Using a point-kernel convolution, the mean absorbed dose to each organ from the individual contributions of each source organ were calculated. S factor equivalent values were obtained by assuming a uniform distribution of radioactivity in each organ. Results were validated by comparing 3D-ID generated electron S factors for different-sized spheres with published data. Depending on matrix size, sphere size, and radionuclide, 1% (256(2) matrix) to 18% (64(2) matrix) agreement was obtained. RESULTS: S factor values were calculated for liver, spleen, and right and left kidneys. Cross-organ electron-absorbed fractions of up to 0.33 were obtained (e.g., (90)Y right kidney to liver). Comparisons between S factor values and values obtained assuming complete absorption of electron energy yielded differences of more than 190% ((90)Y spleen self-dose). CONCLUSION: The effect of cross-organ and self-absorbed dose is dependent on emission energy and organ geometry and should be considered in murine dose estimates. The approach used to generate these S factors is applicable to other animal systems and also to nonuniform activity distributions that may be obtained by small-animal SPECT or PET imaging or by quantitative autoradiography.

Animals↗

PubMed2003

Pharmacokinetics and Biodistribution of (86)Y-Trastuzumab for (90)Y dosimetry in an ovarian carcinoma model: correlative MicroPET and MRI.

UNLABELLED: Preclinical biodistribution and pharmacokinetics of investigational radiopharmaceuticals are typically obtained by longitudinal animal studies. These have required the sacrifice of multiple animals at each time point. Advances in small-animal imaging have made it possible to evaluate the biodistribution of radiopharmaceuticals across time in individual animals, in vivo. MicroPET and MRI-based preclinical biodistribution and localization data were obtained and used to assess the therapeutic potential of (90)Y-trastuzumab monoclonal antibody (mAb) (anti-HER2/neu) against ovarian carcinoma. METHODS: Female nude mice were inoculated intraperitoneally with 5.10(6) ovarian carcinoma cells (SKOV3). Fourteen days after inoculation, 12-18 MBq (86)Y-labeled trastuzumab mAb was injected intraperitoneally. Tumor-free mice, injected with (86)Y-trastuzumab, and tumor-bearing mice injected with labeled, irrelevant mAb or (86)Y-trastuzumab + 100-fold excess unlabeled trastuzumab were used as controls. Eight microPET studies per animal were collected over 72 h. Standard and background images were collected for calibration. MicroPET images were registered with MR images acquired on a 1.5-T whole-body MR scanner. For selected time points, 4.7-T small-animal MR images were also obtained. Images were analyzed and registered using software developed in-house. At completion of imaging, suspected tumor lesions were dissected for histopathologic confirmation. Blood, excised normal organs, and tumor nodules were measured by gamma-counting. Tissue uptake was expressed relative to the blood concentration (percentage of injected activity per gram of tissue [%IA/g]/%IA/g blood). (86)Y-Trastuzumab pharmacokinetics were used to perform (90)Y-trastuzumab dosimetry. RESULTS: Intraperitoneal injection of mAb led to rapid blood-pool uptake (5-9 h) followed by tumor localization (26-32 h), as confirmed by registered MR images. Tumor uptake was greatest for (86)Y-trastuzumab (7 +/- 1); excess unlabeled trastuzumab yielded a 70% reduction. Tumor uptake for the irrelevant mAb was 0.4 +/- 0.1. The concentration in normal organs relative to blood ranged from 0 to 1.4 across all studies, with maximum uptake in spleen. The absorbed dose to the kidneys was 0.31 Gy/MBq (90)Y-trastuzumab. The liver received 0.48 Gy/MBq, and the spleen received 0.56 Gy/MBq. Absorbed dose to tumors varied from 0.10 Gy/MBq for radius = 0.1 mm to 3.7 Gy/MBq for radius = 5 mm. CONCLUSION: For all injected compounds, the relative microPET image intensity of the tumor matched the subsequently determined (86)Y uptake. Coregistration with MR images confirmed the position of (86)Y uptake relative to various organs. Radiolabeled trastuzumab mAb was shown to localize to sites of disease with minimal normal organ uptake. Dosimetry calculations showed a strong dependence on tumor size. These results demonstrate the usefulness of combined microPET and MRI for the evaluation of novel therapeutics.

Animals↗

PubMed2002

Simultaneous perfusion and BOLD imaging using reverse spiral scanning at 3T: characterization of functional contrast and susceptibility artifacts.

Reverse spiral scanning with arterial spin-labeling was developed at 3T to simultaneously detect perfusion and BOLD signals in the brain by subtracting or adding the control and labeled images, respectively, in the same dataset. BOLD contrast was improved with the longer effective echo time achieved in the reverse spiral scan compared to conventional forward spiral scans. Susceptibility artifacts near air-tissue interfaces in the brain were substantially reduced in the reverse spiral images due to their early data acquisition time and, hence, less signal attenuation. Brain activation experiments with the reverse spiral scan were performed on normal subjects and were compared to forward spiral imaging in the same subjects. The experiments demonstrated that reverse spiral imaging was able to detect perfusion and BOLD signals simultaneously and reliably, even in the brain regions with severe susceptibility-induced local gradients, while forward spiral scans were either not optimal for detecting the two functional signals at the same time or were vulnerable to susceptibility artifacts.

Adult↗

PubMed2002

Single-shot interleaved z-shim EPI with optimized compensation for signal losses due to susceptibility-induced field inhomogeneity at 3 T.

A new single-shot echo-planar imaging (EPI) sequence with interleaved z-shim and optimized compensation for susceptibility-induced signal loss is proposed in this paper. Experiments on human brain demonstrated that the new method is able to regain signal dropout in brain areas with severe susceptibility-induced local gradients, while its image acquisition speed is comparable to that of conventional single-shot EPI techniques. Significant signal-to-noise ratio improvements were demonstrated in the ventral prefrontal and lateral temporal lobes with the new technique compared to a conventional EPI. Brain activation experiments with a bilateral finger-tapping task were performed with intentionally introduced local gradients near the left sensorimotor cortex, by a small gadolinium (Gd)-doped bottle placed on the left side of the head. The results of the functional experiments showed that the interleaved z-shim EPI sequence effectively recovered the signal loss caused by the Gd-doped bottle and reliably detected activation signals in bilateral sensorimotor regions, while the activation signals on the left side diminished considerably in a conventional EPI technique. The new technique, with the capability of reducing susceptibility artifacts and rapid scanning speed, may be particularly useful for event-related functional MRI experiments in the base of the brain, which are of great importance in neuropsychiatric studies.

Adult↗

PubMedDate not supplied

MRI of mouse models for gliomas shows similarities to humans and can be used to identify mice for preclinical trials.

Magnetic resonance imaging (MRI) has been utilized for screening and detecting brain tumors in mice based upon their imaging characteristics appearance and their pattern of enhancement. Imaging of these tumors reveals many similarities to those observed in humans with identical pathology. Specifically, high-grade murine gliomas have histologic characteristics of glioblastoma multiforme (GBM) with contrast enhancement after intravenous administration of gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA), implying disruption of the blood-brain barrier in these tumors. In contrast, low-grade murine oligodendrogliomas do not reveal contrast enhancement, similar to human tumors. MRI can be used to identify mice with brain neoplasms as inclusion criteria in preclinical trials.

Animals↗