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Biomedical subjects

Raymond C Chan

Publications and source records attributed to Raymond C Chan.

15 recordsLinked to original sources
PubMed2006

Comprehensive volumetric optical microscopy in vivo.

Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects.

Angioplasty↗
PubMed2006

Arterial wall imaging: evaluation with 16-section multidetector CT in blood vessel phantoms and ex vivo coronary arteries.

PURPOSE: To evaluate the diagnostic performance of 16-section multidetector computed tomography (CT) for assessment of plaques in phantoms and ex vivo coronary arteries, with intravascular ultrasonography (US) and optical coherence tomography (OCT) as reference standards. MATERIALS AND METHODS: Research protocol was HIPAA compliant and approved by institutional review board, without informed consent required. Blood vessel and lesion composition phantoms and ex vivo coronary arteries were imaged with 16-section CT. Wall areas of phantoms and ex vivo coronary arteries were measured with multidetector CT and intravascular US. Sensitivity and specificity for lipid detection were determined in lesion composition phantoms. CT numbers of blood vessel wall were determined in ex vivo coronary arteries and compared with lesion classification results from OCT. Agreement in dimensional measurements was compared (paired t tests). CT numbers within blood vessel wall of CT cross sections classified as lipid rich, fibrous, and calcified at OCT were compared (Kruskal-Wallis tests). RESULTS: Mean blood vessel wall areas measured with CT and US in phantoms were 9.2 mm(2) +/- 1.8 (standard deviation) and 10.4 mm(2) +/- 3.4 (bias, -1.3 mm(2) +/- 3.1; P < .05), respectively. Mean blood vessel wall areas measured in ex vivo coronary arteries with CT and US were 10.9 mm(2) +/- 4.1 and 9.1 mm(2) +/- 3.1 (bias, 1.8 mm(2) +/- 3.0; P < .001), respectively. Sensitivity and specificity of 93% and 92%, respectively, for identification of lipid-rich lesions were observed in lesion composition phantoms. Mean CT numbers in blood vessel wall of ex vivo coronary arteries identified at OCT as predominantly lipid rich, fibrous, and calcified were 29 HU +/- 43, 101 HU +/- 21, and 135 HU +/- 199, respectively (P < .001). CONCLUSION: Determination of composition of individual plaques from attenuation values can be more challenging because of overlapping values for different tissue types.

Coronary Angiography↗
PubMed2006

Bright and black blood imaging of the carotid bifurcation at 3.0T.

PURPOSE: The aim of this study was to evaluate our preliminary experience at 3.0 T with imaging of the carotid bifurcation in healthy and atherosclerotic subjects. Application at 3.0 T is motivated by the signal-to-noise gain for improving spatial resolution and reducing signal averaging requirements. MATERIALS AND METHODS: We utilized a dual phased array coil and applied 2D, 3D time of flight (TOF) and turbo spin echo (TSE) sequences with comparison of two lumen signal suppression methods for black blood (BB) TSE imaging including double inversion preparation (DIR) and spatial presaturation pulses. The signal-to-noise ratios (SNR) of healthy carotid vessel walls were compared in 2D and 3D BB TSE acquisitions. The bright and black blood multi-contrast exam was demonstrated for a complex carotid plaque. RESULTS: Contrast-to-noise (CNR) greater than 150 was achieved between the lumen and suppressed background for 3D TOF. For BB, both methods provided sufficient lumen signal suppression but slight residual flow artifacts remained at the bifurcation level. As expected 3D TSE images had higher SNR compared to 2D, but increased motion sensitivity is a significant issue for 3D at high field. For multi-contrast imaging of atherosclerotic plaque, fibrous, calcified and lipid components were resolved. The CNR ratio of fibrous (bright on PDW, T2W) and calcified (dark in T1W, T2W, PDW) plaque components was maximal in the T2W images. The 3D TOF angiogram indicating a 40% stenosis was complemented by 3D multi-planar reformat of BB images that displayed plaque extent. Detection of intimal thickening, the earliest change associated with atherosclerotic progression was observed in BB PDW images at 3.0 T. CONCLUSIONS: High SNR and CNR images have been demonstrated for the healthy and diseased carotid. Improvements in RF coils along with pulse sequence optimization, and evaluation of endogenous and exogenous contrast mechanisms will further enhance carotid imaging at 3.0T.

Adult↗
PubMed2006

Improved vessel morphology measurements in contrast-enhanced multi-detector computed tomography coronary angiography with non-linear post-processing.

Multi-detector computed tomography (MDCT) permits detection of coronary plaque. However, noise and blurring impair accuracy and precision of plaque measurements. The aim of the study was to evaluate MDCT post-processing based on non-linear image deblurring and edge-preserving noise suppression for measurements of plaque size. Contrast-enhanced MDCT coronary angiography was performed in four subjects (mean age 55 +/- 5 years, mean heart rate 54 +/- 5 bpm) using a 16-slice scanner (Siemens Sensation 16, collimation 16 x 0.75 mm, gantry rotation 420 ms, tube voltage 120 kV, tube current 550 mAs, 80 mL of contrast). Intravascular ultrasound (IVUS; 40 MHz probe) was performed in one vessel in each patient and served as a reference standard. MDCT vessel cross-sectional images (1 mm thickness) were created perpendicular to centerline and aligned with corresponding IVUS images. MDCT images were processed using a deblurring and edge-preserving noise suppression algorithm. Then, three independent blinded observers segmented lumen and outer vessel boundaries in each modality to obtain vessel cross-sectional area and wall area in the unprocessed MDCT cross-sections, post-processed MDCT cross-sections and corresponding IVUS. The wall area measurement difference for unprocessed and post-processed MDCT images relative to IVUS was 0.4 +/- 3.8 mm2 and -0.2 +/- 2.2 mm2 (p < 0.05), respectively. Similarly, Bland-Altman analysis of vessel cross-sectional area from unprocessed and post-processed MDCT images relative to IVUS showed a measurement difference of 1.0 +/- 4.4 and 0.6 +/- 4.8 mm2, respectively. In conclusion, MDCT permitted accurate in vivo measurement of wall area and vessel cross-sectional area as compared to IVUS. Post-processing to reduce blurring and noise reduced variability of wall area measurements and reduced measurement bias for both wall area and vessel cross-sectional area.

Algorithms↗
PubMed2005

Tissue elasticity estimation with optical coherence elastography: toward mechanical characterization of in vivo soft tissue.

High-resolution imaging provides a significant means for accurate material modulus estimation and mechanical characterization. Within the realm of in vivo soft tissue characterization, particularly on small biological length scales such as arterial atherosclerotic plaques, optical coherence tomography (OCT) offers a desirable imaging modality with higher spatial resolution and contrast of tissue as compared with intravascular ultrasound (IVUS). Based on recent advances in OCT imaging and elastography, we present a fully integrated system for tissue elasticity reconstruction, and assess the benefits of OCT on the distribution results of four representative tissue block models. We demonstrate accuracy, with displacement residuals on the order of 10(-6) mm (more than 3 orders of magnitude less than average calculated displacements), and high-resolution estimates, with the ability to resolve inclusions of 0.15 mm diameter.

Angiography↗
PubMed2004

Integration of cardiac magnetic resonance imaging with three-dimensional electroanatomic mapping to guide left ventricular catheter manipulation: feasibility in a porcine model of healed myocardial infarction.

OBJECTIVES: In a series of in vitro and in vivo experiments, we evaluated the feasibility of integrating three-dimensional (3D) magnetic resonance imaging (MRI) and electroanatomic mapping (EAM) data to guide real-time left ventricular (LV) catheter manipulation. BACKGROUND: Substrate-based catheter ablation of post-myocardial infarction ventricular tachycardia requires delineation of the scarred myocardium, typically using an EAM system. Cardiac MRI might facilitate this procedure by localizing this myocardial scar. METHODS: A custom program was employed to integrate 3D MRI datasets with real-time EAM. Initially, a plastic model of the LV was used to determine the optimal alignment/registration strategy. To determine the in vivo accuracy of the registration process, ablation lesions were directed at iatrogenic MRI-visible "targets" (iron oxide injections) within normal porcine LVs (n = 5). Finally, this image integration strategy was assessed in a porcine infarction model (n = 6) by targeting ablation lesions to the scar border. RESULTS: The in vitro experiments revealed that registration of the LV alone results in inaccurate alignment due primarily to rotation along the chamber's long axis. Inclusion of the aorta in the registration process rectified this error. In the iron oxide injection experiments, the ablation lesions were 1.8 +/- 0.5 mm from the targets. In the porcine infarct model, the catheter could be reliably navigated to the mitral valve annulus, and the ablation lesions were uniformly situated at the scar borders. CONCLUSIONS: These data suggest that registration of pre-acquired magnetic resonance images with real-time mapping is sufficiently accurate to guide LV catheter manipulation in a reliable and clinically relevant manner.

Animals↗
PubMed2004

Condensin restructures chromosomes in preparation for meiotic divisions.

The production of haploid gametes from diploid germ cells requires two rounds of meiotic chromosome segregation after one round of replication. Accurate meiotic chromosome segregation involves the remodeling of each pair of homologous chromosomes around the site of crossover into a highly condensed and ordered structure. We showed that condensin, the protein complex needed for mitotic chromosome compaction, restructures chromosomes during meiosis in Caenorhabditis elegans. In particular, condensin promotes both meiotic chromosome condensation after crossover recombination and the remodeling of sister chromatids. Condensin helps resolve cohesin-independent linkages between sister chromatids and alleviates recombination-independent linkages between homologues. The safeguarding of chromosome resolution by condensin permits chromosome segregation and is crucial for the formation of discrete, individualized bivalent chromosomes.

Adenosine Triphosphatases↗
PubMed2004

Mechanical analysis of atherosclerotic plaques based on optical coherence tomography.

Finite element analysis is a powerful tool for investigating the biomechanics of atherosclerosis and has thereby provided an improved understanding of acute myocardial infarction. Structural analysis of arterial walls is traditionally performed using geometry contours derived from histology. In this paper we demonstrate the first use of a new imaging technique, optical coherence tomography (OCT), as a basis for finite element analysis. There are two primary benefits of OCT relative to histology: 1) imaging is performed without excessive tissue handling, providing a more realistic geometry than histology and avoiding structural artifacts common to histologic processing, and 2) OCT imaging can be performed in vivo, making it possible to study disease progression and the effect of therapeutic treatments in animal models and living patients. Patterns of mechanical stress and strain distributions computed from finite element analysis based on OCT were compared with those from modeling based on "gold standard" histology. Our results indicate that vascular structure and composition determined by OCT provides an adequate basis for investigating the biomechanical factors relevant to atherosclerosis and acute myocardial infarction.

Coronary Artery Disease↗
PubMed2003

Chromosome cohesion is regulated by a clock gene paralogue TIM-1.

Faithful transmission of the genome requires that a protein complex called cohesin establishes and maintains the regulated linkage between replicated chromosomes before their segregation. Here we report the unforeseen participation of Caenorhabditis elegans TIM-1, a paralogue of the Drosophila clock protein TIMELESS, in the regulation of chromosome cohesion. Our biochemical experiments defined the C. elegans cohesin complex and revealed its physical association with TIM-1. Functional relevance of the interaction was demonstrated by aberrant mitotic chromosome behaviour, embryonic lethality and defective meiotic chromosome cohesion caused by the disruption of either TIM-1 or cohesin. TIM-1 depletion prevented the assembly of non-SMC (structural maintenance of chromosome) cohesin subunits onto meiotic chromosomes; however, unexpectedly, a partial cohesin complex composed of SMC components still loaded. Further disruption of cohesin activity in meiosis by the simultaneous depletion of TIM-1 and an SMC subunit decreased homologous chromosome pairing before synapsis, revealing a new role for cohesin in metazoans. On the basis of comparisons between TIMELESS homologues in worms, flies and mice, we propose that chromosome cohesion, rather than circadian clock regulation, is the ancient and conserved function for TIMELESS-like proteins.

Animals↗
PubMed2003

Coronary calcium quantification using various calibration phantoms and scoring thresholds.

RATIONALE AND OBJECTIVES: To compare scoring threshold and calibration method-dependent accuracy and variability of coronary calcium measurements by multidetector computed tomography (MDCT). METHODS: Ninety-five subjects were scanned with MDCT. We calculated Agatston score and volume score. Mineral mass (MM) was calculated using patient-based and scanner-based calibration methods. Accuracy of calibration was validated using artificial calcium cylinders. RESULTS: Patient-based and scanner-based calibration permitted accurate quantification of artificial calcium cylinders (bias: 0 mg and -2 mg). In the subjects, the mean relative difference of MM measurements performed at 90 and 130 Hounsfield units threshold (59%) was lower than for Agatston score (94%) and volume score (109%; P < 0.05). Patient-based and scanner-based calibration yielded systematically different MM measurements (bias: 22%). CONCLUSIONS: MM lowers threshold-dependent variability of coronary calcium measurements. Patient-based and scanner-based calibration allows accurate calcium quantification ex vivo but reveal systematic differences in subjects. Patient-based calibration may better account for subject size and composition.

Aged↗
PubMed2002

A molecular link between gene-specific and chromosome-wide transcriptional repression.

Gene-specific and chromosome-wide mechanisms of transcriptional regulation control development in multicellular organisms. SDC-2, the determinant of hermaphrodite fate in Caenorhabditis elegans, is a paradigm for both modes of regulation. SDC-2 represses transcription of X chromosomes to achieve dosage compensation, and it also represses the male sex-determination gene her-1 to elicit hermaphrodite differentiation. We show here that SDC-2 recruits the entire dosage compensation complex to her-1, directing this X-chromosome repression machinery to silence an individual, autosomal gene. Functional dissection of her-1 in vivo revealed DNA recognition elements required for SDC-2 binding, recruitment of the dosage compensation complex, and transcriptional repression. Elements within her-1 differed in location, sequence, and strength of repression, implying that the dosage compensation complex may regulate transcription along the X chromosome using diverse recognition elements that play distinct roles in repression.

Animals↗