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In JoVE (1)
Other Publications (32)
- Human Brain Mapping
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
- Academic Radiology
- Journal of Magnetic Resonance Imaging : JMRI
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
- Journal of Cataract and Refractive Surgery
- Magnetic Resonance Imaging
- Spine
- NeuroImage
- Journal of Magnetic Resonance Imaging : JMRI
- IEEE Transactions on Medical Imaging
- Chemico-biological Interactions
- Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine
- Annals of Biomedical Engineering
- Cancer Cell International
- Computerized Medical Imaging and Graphics : the Official Journal of the Computerized Medical Imaging Society
- Medical Engineering & Physics
- Optics Express
- Medical Image Computing and Computer-assisted Intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention
- Contrast Media & Molecular Imaging
- Australasian Physical & Engineering Sciences in Medicine / Supported by the Australasian College of Physical Scientists in Medicine and the Australasian Association of Physical Sciences in Medicine
- Journal of Magnetic Resonance Imaging : JMRI
- Biomedical Optics Express
- Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie
- Contrast Media & Molecular Imaging
- Optics Express
- Optics Letters
- Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
- Biomedical Optics Express
- Computerized Medical Imaging and Graphics : the Official Journal of the Computerized Medical Imaging Society
- Journal of Biomedical Optics
- Journal of Neurology, Neurosurgery, and Psychiatry
Articles by Kelvin K. Wong in JoVE
Bioluminescence Imaging of Heme Oxygenase-1 Upregulation in the Gua Sha Procedure
Kenneth K. Kwong1,2, Lenuta Kloetzer1,2,3,4, Kelvin K. Wong5,6, Jia-Qian Ren1,2, Braden Kuo1,2,3,4, Yan Jiang7, Y. Iris Chen1,2, Suk-Tak Chan1,2,8, Geoffrey S. Young9, Stephen T.C. Wong5,6
1Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 2Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, 3Gastrointestinal Unit, Massachusetts General Hospital, Harvard Medical School, 4Department of Medicine, Massachusetts General Hospital, Harvard Medical School, 5Center for biotechnology and Informatics, The Methodist Hospital Research Institute, 6Department of Radiology, The Methodist Hospital, Weill Cornell Medical College, 7Bejing University of Chinese Medicine, 8Department of Health Technology and Informatics, The Hong Kong Polytechnic University, 9Department of Radiology, Brigham and Women's Hospital, Harvard Medical School
Gua Sha, traditional Chinese therapeutic skin scraping, causes subcutaneous microvascular blood extravasation. We report a protocol of bioluminescence imaging of HO-1-luciferase transgenic mice to demonstrate that Gua Sha upregulates heme oxygenase-1 (HO-1) in multiple organs.
Other articles by Kelvin K. Wong on PubMed
An FMRI Study Comparing Brain Activation Between Word Generation and Electrical Stimulation of Language-implicated Acupoints
Human Brain Mapping. Mar, 2003 | Pubmed ID: 12599282
We compared the brain activation on functional magnetic resonance imaging (MRI) during word generation with the activation during electrical stimulation of two language-implicated acupoints in 17 healthy, Mandarin-speaking, Chinese male volunteers (age 19-26 years). All subjects were strongly right handed according to a handedness inventory. Using a standard functional MRI procedure and a word-generation paradigm, significant activation was seen in the left and right inferior frontal gyri (BA 44, 45) as well as the left superior temporal gyrus (BA 22, 42). Stronger activation with a larger volume was seen in the left hemisphere. Electrical stimulation of either one of the two language-implicated acupoints, SJ 8 (11 subjects) and Du 15 (6 subjects), without the word-generation paradigm in the same cohort, produced significant activation in the right inferior frontal gyrus (BA 44, 46) and in the left and right superior temporal gyri (BA 22, 42), respectively. Nevertheless, no activation was seen in the left inferior frontal gyrus. In addition, electrical stimulation of the adjacent non-acupoints did not produce any significant brain activation. Although our results support the notion of acupoint-brain activation, applying acupuncture at SJ 8 or Du 15 does not activate the typical language areas in the left inferior frontal cortex.
High-resolution in Vivo CBV Mapping with MRI in Wild-type Mice
Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Apr, 2003 | Pubmed ID: 12652549
NMR microimaging has the potential to elucidate cerebrovascular abnormalities in mouse models. In this study, the relative regional cerebral blood volume (CBV) map is presented for C57BL6/J wild-type mice. The CBV mapping was based on changes in the steady-state NMR transverse relaxation rate (DeltaR(2)) associated with the presence of a superparamagnetic intravascular contrast agent (MION) with a long blood halflife. The experiments were performed at 9.4 T at a voxel size of 100 microm x 100 microm x 600 microm. Fine details, such as the hippocampal and olfactory bulb area, were visualized in the CBV map. The relative regional CBV values of various brain regions were measured. The DeltaR(2) dosage dependency and MION tissue clearance in mouse are also reported.
Superconducting RF Coils for Clinical MR Imaging at Low Field
Academic Radiology. Sep, 2003 | Pubmed ID: 13678086
A number of recent reports in the MRI literature have established that substantial signal-to-noise ratio (SNR) gains can be achieved with small samples or low resonance frequencies, through the use of high-quality factor high-temperature superconducting (HTS) RF receive coils. We show the application of HTS coils to the imaging of human subjects with improved SNR compared with copper coils.
Mapping Cyclic Change of Regional Myocardial Blood Volume Using Steady-state Susceptibility Effect of Iron Oxide Nanoparticles
Journal of Magnetic Resonance Imaging : JMRI. Jan, 2004 | Pubmed ID: 14696220
To demonstrate an in vivo magnetic resonance imaging (MRI) technique that maps the cyclic change of regional myocardial blood volume (MBV) during the cardiac cycle.
In Vivo Study of Microbubbles As an MR Susceptibility Contrast Agent
Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Sep, 2004 | Pubmed ID: 15334560
The potential application of gas microbubbles as a unique intravascular susceptibility contrast agent for MRI has not been fully explored. In this study, the MR susceptibility effect of an ultrasound microbubble contrast agent, Optison, was studied with rat liver imaging at 7 T. Optison suspension in two different doses (0.15 mL/kg and 0.4 mL/kg) was injected into rats, and induced transverse relaxation rate increases (deltaR2*) of 29.1 +/- 1.6 s(-1) (N = 2) and 61.5 +/- 12.9 s(-1) (N = 6), respectively, in liver tissue. Liver uptake of intact albumin microbubbles was observed 10 min after injection. Eight of the 16 rats studied showed no susceptibility enhancement. This is probably attributable to the intravascular microbubble growth due to transmural CO2 supersaturation in the cecum and colon in small animals that causes microbubble aggregation and trapping in the inferior vena cava (IVC). In vitro deltaR2* measurements of Optison suspension at different concentrations are also reported.
Suprachoroidal Hemorrhage During Cataract Surgery in a Vitrectomized Eye
Journal of Cataract and Refractive Surgery. Jun, 2005 | Pubmed ID: 16039505
We report a case of surprachoroidal hemorrhage (SCH) that occurred during cataract surgery in a previously vitrectomized eye. The only sign of SCH was a progressive shadow obscuring the red reflex. There was no increase in intraocular pressure (IOP), shallowing of the anterior chamber, or iris prolapse. Postoperatively, the SCH gradually resolved without complications, leaving a series of subretinal pigmentary lines. Surgeons should be aware that the signs normally expected in SCH may not develop in vitrectomized eyes. Obscuration of the red reflex may be the only sign of the hemorrhage, and when this happens, it may be prudent to keep the IOP elevated and suture the incision at the end of the procedure.
Spinal Effects of Acupuncture Stimulation Assessed by Proton Density-weighted Functional Magnetic Resonance Imaging at 0.2 T
Magnetic Resonance Imaging. Dec, 2005 | Pubmed ID: 16376183
Signal changes can be detected by proton density-weighted functional imaging in both the brain and the spinal cord. These are attributed to changes in extravascular water proton (signal enhancement by extravascular protons) density during neuronal activation. In this study, we used this technique to detect correlations between acupoint stimulation and neural activity in the spinal cord. Stimulation of acupoints associated with treatment of sensorimotor deficits (LI4 and LI11) was performed on 11 volunteers. During stimulation, 8 of the 11 subjects had consistent functional activations in C6/C7. A bilateral activation pattern was common. Our findings show that acupoint stimulation modulates activity in the spinal cord.
Association of the Taq I Allele in Vitamin D Receptor with Degenerative Disc Disease and Disc Bulge in a Chinese Population
Spine. May, 2006 | Pubmed ID: 16648751
Large scale, case-control study.
Proton-density-weighted Spinal FMRI with Sensorimotor Stimulation at 0.2 T
NeuroImage. Feb, 2006 | Pubmed ID: 16140548
Proton-density-weighted fMRI at low field (0.2 T) was carried out in the cervical spinal cord of healthy volunteers in this study to examine the feasibility of detecting proton density alteration accompanying activation in the spinal cord. Subjects were asked to grip both hands simultaneously, providing sensorimotor simulation for spinal fMRI. Over 70% subjects recruited had activation localized at C6-C7 spinal levels with discrete activation detected in both the anterior and posterior horns of the cervical spinal cord, and the average fractional signal change was 4.06%. The 0.2 T low magnetic field and the 24 ms short TE used in this study diminished the BOLD effect to a negligible level, thus the observed signal change was believed to be mainly attributable to proton density increase during neuronal stimulation. Our results suggested the existence of task-driven proton density change in the cervical spinal cord.
First-pass Myocardial Perfusion Image Registration by Maximization of Normalized Mutual Information
Journal of Magnetic Resonance Imaging : JMRI. Mar, 2008 | Pubmed ID: 18183575
To evaluate a left ventricular image registration algorithm for first-pass MR myocardial perfusion.
Simultaneous Ultrasound and MRI System for Breast Biopsy: Compatibility Assessment and Demonstration in a Dual Modality Phantom
IEEE Transactions on Medical Imaging. Feb, 2008 | Pubmed ID: 18334446
Simultaneous capturing of ultrasound (US) and magnetic resonance (MR) images allows fusion of information obtained from both modalities. We propose an MR-compatible US system where MR images are acquired in a known orientation with respect to the US imaging plane and concurrent real-time imaging can be achieved. Compatibility of the two imaging devices is a major issue in the physical setup. Tests were performed to quantify the radio frequency (RF) noise introduced in MR and US images, with the US system used in conjunction with MRI scanner of different field strengths (0.5 T and 3 T). Furthermore, simultaneous imaging was performed on a dual modality breast phantom in the 0.5 T open bore and 3 T close bore MRI systems to aid needle-guided breast biopsy. Fiducial based passive tracking and electromagnetic based active tracking were used in 3 T and 0.5 T, respectively, to establish the location and orientation of the US probe inside the magnet bore. Our results indicate that simultaneous US and MR imaging are feasible with properly-designed shielding, resulting in negligible broadband noise and minimal periodic RF noise in both modalities. US can be used for real time display of the needle trajectory, while MRI can be used to confirm needle placement.
Anti-acetylcholinesterase Activities of Traditional Chinese Medicine for Treating Alzheimer's Disease
Chemico-biological Interactions. Sep, 2008 | Pubmed ID: 18573242
Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. It is the most common type of dementia in the ageing population due to a severe loss of cholinergic neurons in selected brain area. At present, acetylcholinesterase inhibitors (AChEI) are the first group of drugs approved by the FDA to treat mild to moderate Alzheimer's disease. Most of these drugs such as huperzine and galanthamine are originally isolated from plants. In this study, the AChE inhibitory activities from extracts of Chinese medicinal herbs that have traditionally been prescribed to treat insomnia and brain function disorders were examined in a 96-well plate assay based on Ellman's method. Both ethanol and aqueous extracts of 26 traditional Chinese medicinal herbs were tested. Inhibitory effects were expressed as the percentage of inhibition. For the herbal extracts that were shown to exert a significant inhibition, dose-dependent inhibitory assays were also performed. Ethanol and aqueous extracts of six herbs were found to have high AChE inhibitory activities in a dose-dependent manner. The IC(50) of these herbal extracts on inhibition of AChE are at around 5-85 microm/ml. The results of this study indicate that there is a great potential to search for novel usage of these medicinal herbs for the treatment of AD.
Improved Residue Function and Reduced Flow Dependence in MR Perfusion Using Least-absolute-deviation Regularization
Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine / Society of Magnetic Resonance in Medicine. Feb, 2009 | Pubmed ID: 19161133
Cerebral blood flow (CBF) estimates derived from singular value decomposition (SVD) of time intensity curves from Gadolinium bolus perfusion-weighted imaging are known to underestimate CBF, especially at high flow rates. We report the development of a model-independent delay-invariant deconvolution technique using least-absolute-deviation (LAD) regularization to improve the CBF estimation accuracy. Computer simulations were performed to compare the accuracy of CBF estimates derived from LAD, reformulated SVD (rSVD) and standard SVD (sSVD) techniques. Simulations were performed at image signal-to-noise ratios ranging from 20 to 400, cerebral blood volumes from 1% to 10%, and CBF from 2.5 mL/100 g/min to 176.5 mL/100 g/min to estimate the effect of these parameters on the accuracy of CBF estimation. The LAD method improved the CBF estimation accuracy by up to 32% in gray matter and 23% in white matter compared with rSVD and sSVD methods. LAD method also reduces the systematic bias of rSVD and sSVD methods to baseline SNR while producing more accurate and reproducible residue function calculation than either rSVD or sSVD method. Initial clinical implementation of the method on six representative clinical cases confirm the advantages of the LAD method over rSVD and sSVD methods.
Cardiac Flow Analysis Applied to Phase Contrast Magnetic Resonance Imaging of the Heart
Annals of Biomedical Engineering. Aug, 2009 | Pubmed ID: 19466548
Phase contrast magnetic resonance imaging is performed to produce flow fields of blood in the heart. The aim of this study is to demonstrate the state of change in swirling blood flow within cardiac chambers and to quantify it for clinical analysis. Velocity fields based on the projection of the three dimensional blood flow onto multiple planes are scanned. The flow patterns can be illustrated using streamlines and vector plots to show the blood dynamical behavior at every cardiac phase. Large-scale vortices can be observed in the heart chambers, and we have developed a technique for characterizing their locations and strength. From our results, we are able to acquire an indication of the changes in blood swirls over one cardiac cycle by using temporal vorticity fields of the cardiac flow. This can improve our understanding of blood dynamics within the heart that may have implications in blood circulation efficiency. The results presented in this paper can establish a set of reference data to compare with unusual flow patterns due to cardiac abnormalities. The calibration of other flow-imaging modalities can also be achieved using this well-established velocity-encoding standard.
Bioluminescence Imaging Reveals Inhibition of Tumor Cell Proliferation by Alzheimer's Amyloid Beta Protein
Cancer Cell International. 2009 | Pubmed ID: 19480719
Cancer and Alzheimer's disease (AD) are two seemingly distinct diseases and rarely occur simultaneously in patients. To explore molecular determinants differentiating pathogenic routes towards AD or cancer, we investigate the role of amyloid beta protein (Abeta) on multiple tumor cell lines that are stably expressing luciferase (human glioblastoma U87; human breast adenocarcinoma MDA-MB231; and mouse melanoma B16F).
Introduction to the Special Issue of Image-guided Surgical Planning and Therapy
Computerized Medical Imaging and Graphics : the Official Journal of the Computerized Medical Imaging Society. Jan, 2010 | Pubmed ID: 19775868
Cardiac Flow Component Analysis
Medical Engineering & Physics. Mar, 2010 | Pubmed ID: 20022796
In a chamber of the heart, large-scale vortices are shown to exist as the result of the dynamic blood flow and unique morphological changes of the chamber wall. As the cardiovascular flow varies over a cardiac cycle, there is a need for a robust quantification method to analyze its vorticity and circulation. We attempt to measure vortex characteristics by means of two-dimensional vorticity maps and vortex circulation. First, we develop vortex component analysis by segmenting the vortices using an data clustering algorithm before histograms of their vorticity distribution are generated. The next stage is to generate the statistics of the vorticity maps for each phase of the cardiac cycle to allow analysis of the flow. This is followed by evaluating the circulation of each segmented vortex. The proposed approach is dedicated to examining vortices within the human heart chamber. The vorticity field can indicate the strength and number of large-scale vortices in the chamber. We provide the results of the flow analysis after vorticity map segmentation and the statistical properties that characterize the vorticity components. The success of the cardiac measurement and analysis is illustrated by a case study of the right atrium. Our investigation shows that it is possible to utilize a data clustering algorithm to segment vortices after vorticity mapping, and that the vorticity and circulation analysis of a chamber vorticity can provide new insights into the blood flow within the cardiovascular structure.
Delivery of Picosecond Lasers in Multimode Fibers for Coherent Anti-Stokes Raman Scattering Imaging
Optics Express. Jun, 2010 | Pubmed ID: 20588430
We investigated the possibility of using standard commercial multimode fibers (MMF), Corning SMF28 fibers, to deliver picosecond excitation lasers for coherent anti-Stokes Raman scattering (CARS) imaging. We theoretically and/or experimentally analyzed issues associated with the fiber delivery, such as dispersion length, walk-off length, nonlinear length, average threshold power for self-phase modulations, and four-wave mixing (FWM). These analyses can also be applied to other types of fibers. We found that FWM signals are generated in MMF, but they can be filtered out using a long-pass filter for CARS imaging. Finally, we demonstrated that MMF can be used for delivery of picosecond excitation lasers in the CARS imaging system without any degradation of image quality.
Motion Artifact Correction of Multi-photon Imaging of Awake Mice Models Using Speed Embedded HMM
Medical Image Computing and Computer-assisted Intervention : MICCAI ... International Conference on Medical Image Computing and Computer-Assisted Intervention. 2010 | Pubmed ID: 20879434
Multi-photon fluorescence microscopy (MFM) captures high-resolution anatomical and functional fluorescence image sequences and can be used for the intact brain imaging of small animals. Recently, it has been extended from imaging anesthetized and head-stabilized animals to awake and head-restrained ones for in vivo neurological study. In these applications, motion correction is an important pre-processing step since brain pulsation and tiny body movement can cause motion artifacts and prevent stable serial image acquisition at such a high spatial resolution. This paper proposes a speed embedded hidden Markov model (SEHMM) for motion correction in MFM imaging of awake head-restrained mice. The algorithm extends the traditional HMM method by embedding a motion prediction model to better estimate the state transition probability. SEHMM is a line-by-line motion correction algorithm, which is implemented within the in-focal-plane 2-D videos and can operate directly on the motion-distorted imaging data without external signal measurements such as the movement, heartbeat, respiration, or muscular tension. In experiments, we demonstrat that SEHMM is more accurate than traditional HMM using both simulated and real MFM image sequences.
Cellular Uptake and Imaging Studies of Gadolinium-loaded Single-walled Carbon Nanotubes As MRI Contrast Agents
Contrast Media & Molecular Imaging. Dec, 2010 | Pubmed ID: 21191979
We quantify here, for the first time, the intracellular uptake (J774A.1 murine macrophage cells) of gadolinium-loaded ultra-short single-walled carbon nanotubes (gadonanotubes or GNTs) in a 3 T MRI scanner using R(2) and R(2)* mapping in vitro. GNT-labeled cells exhibited high and linear changes in net transverse relaxations (ΔR(2) and ΔR(2) (*)) with increasing cell concentration. The measured ΔR(2)* were about three to four times greater than the respective ΔR(2) for each cell concentration. The intracellular uptake of GNTs was validated with inductively coupled plasma optical emission spectrometry (ICP-OES), indicating an average cellular uptake of 0.44 ± 0.09 pg Gd per cell or 1.69 × 10(9) Gd(3+) ions per cell. Cell proliferation MTS assays demonstrated that the cells were effectively labeled, without cytotoxicity, for GNTs concentrations ≤28 µM Gd. In vivo relaxometry of a subcutaneously-injected GNT-labeled cell pellet in a mouse was also demonstrated at 3 T. Finally, the pronounced R(2)* effect of GNT-labeled cells enabled successful in vitro visualization of labeled cells at 9.4 T. Copyright © 2010 John Wiley & Sons, Ltd.
Experimental and Numerical Study on the Hemodynamics of Stenosed Carotid Bifurcation
Australasian Physical & Engineering Sciences in Medicine / Supported by the Australasian College of Physical Scientists in Medicine and the Australasian Association of Physical Sciences in Medicine. Dec, 2010 | Pubmed ID: 21203880
Numerical simulation is performed to demonstrate that hemodynamic factors are significant determinants for the development of a vascular pathology. Experimental measurements by particle image velocimetry are carried out to validate the credibility of the computational approach. We present a study for determining complex flow structures using the case of an anatomically realistic carotid bifurcation model that is reconstructed from medical imaging. A transparent silicone replica of the artery is developed for in-vitro flow measurement. The dynamic behaviours of blood through the vascular structure based on the numerical and experimental approaches show good agreement.
Support Vector Machine Multiparametric MRI Identification of Pseudoprogression from Tumor Recurrence in Patients with Resected Glioblastoma
Journal of Magnetic Resonance Imaging : JMRI. Feb, 2011 | Pubmed ID: 21274970
To automatically differentiate radiation necrosis from recurrent tumor at high spatial resolution using multiparametric MRI features.
Label-free High-resolution Imaging of Prostate Glands and Cavernous Nerves Using Coherent Anti-Stokes Raman Scattering Microscopy
Biomedical Optics Express. 2011 | Pubmed ID: 21483613
A custom built coherent anti-Stokes Raman scattering (CARS) microscope was used to image prostatic glands and nerve structures from 17 patients undergoing radical prostatectomy. Imaging of glandular and nerve structures showed distinctive cellular features that correlated to histological stains. Segmentation of cell nucleus was performed to establish a cell feature-based model to separate normal glands from cancer glands. In this study, we use a single parameter, average cell neighbor distance based on CARS imaging, to characterize normal and cancerous glandular structures. By combining CARS with our novel classification model, we are able to characterize prostate glandular and nerve structures in a manner that potentially enables real-time, intra-operative assessment of surgical margins and neurovascular bundles. As such, this method could potentially improve outcomes following radical prostatectomy.
Caliber Persistent Artery of the Eyelid
Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie. Sep, 2011 | Pubmed ID: 21494872
To report three cases of caliber persistent artery presenting in the eyelid.
Cellular Uptake and Imaging Studies of Gadolinium-loaded Single-walled Carbon Nanotubes As MRI Contrast Agents
Contrast Media & Molecular Imaging. Mar-Apr, 2011 | Pubmed ID: 21504063
We quantify here, for the first time, the intracellular uptake (J774A.1 murine macrophage cells) of gadolinium-loaded ultra-short single-walled carbon nanotubes (gadonanotubes or GNTs) in a 3 T MRI scanner using R(2) and R(2)* mapping in vitro. GNT-labeled cells exhibited high and linear changes in net transverse relaxations (ΔR(2) and ΔR 2*) with increasing cell concentration. The measured ΔR(2)* were about three to four times greater than the respective ΔR(2) for each cell concentration. The intracellular uptake of GNTs was validated with inductively coupled plasma optical emission spectrometry (ICP-OES), indicating an average cellular uptake of 0.44 ± 0.09 pg Gd per cell or 1.69 × 10(9) Gd(3+) ions per cell. Cell proliferation MTS assays demonstrated that the cells were effectively labeled, without cytotoxicity, for GNTs concentrations ≤28 µM Gd. In vivo relaxometry of a subcutaneously-injected GNT-labeled cell pellet in a mouse was also demonstrated at 3 T. Finally, the pronounced R(2)* effect of GNT-labeled cells enabled successful in vitro visualization of labeled cells at 9.4 T.
Coherent Anti-Stokes Raman Scattering Microscopy Imaging with Suppression of Four-wave Mixing in Optical Fibers
Optics Express. Apr, 2011 | Pubmed ID: 21643045
We demonstrated an optical fiber delivered coherent anti-Stokes Raman scattering (CARS) microscopy imaging system with a polarization-based mechanism for suppression of four-wave mixing (FWM) signals in delivery fiber. Polarization maintaining fibers (PMF) were used as the delivery fiber to ensure stability of the state of polarization (SOP) of lasers. The pump and Stokes waves were coupled into PMFs at orthogonal SOPs along the slow and fast axes of PMFs, respectively, resulting in a significant reduction of FWM signals generated in the fiber. At the output end of PMFs, a dual-wavelength waveplate was used to realign the SOPs of the two waves into identical SOPs prior to their entrance into the CARS microscope. Therefore, it allows the pump and Stokes waves with identical SOPs to excite samples at highest excitation efficiency. Our experimental results showed that this polarization-based FWM-suppressing mechanism can dramatically reduce FWM signals generated in PMFs up to approximately 99%. Meanwhile, the PMF-delivered CARS microscopy system with this mechanism can still produce high-quality CARS images. Consequently, our PMF-delivered CARS microscopy imaging system with the polarization-based FWM-suppressing mechanism potentially offers a new strategy for building fiber-based CARS endoscopes with effective suppression of FWM background noises.
Use of Multimode Optical Fibers for Fiber-based Coherent Anti-Stokes Raman Scattering Microendoscopy Imaging
Optics Letters. Aug, 2011 | Pubmed ID: 21808374
A multimode fiber (MMF) was used for both delivery of excitation lasers and collection of returned coherent anti-Stokes Raman scattering (CARS) signals in a CARS microendoscopy prototype imaging system. We demonstrated a polarization-based scheme for suppression of four-wave mixing (FWM) signals in delivery fibers. Our experimental results showed that this polarization-based FWM-suppressing scheme can dramatically reduce FWM signals generated in MMFs, and MMFs can be used to produce CARS images in this microendoscopy system. The proposed MMF-based CARS microendoscopy imaging system with the polarization-based FWM-suppressing scheme offers a potential platform for building fiber-based CARS microendoscopes that can effectively suppress FWM background noises.
Response of Larval Barnacle Proteome to CO(2)-driven Seawater Acidification
Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics. Sep, 2011 | Pubmed ID: 21831737
The majority of benthic marine invertebrates have a complex life cycle, during which the pelagic larvae select a suitable substrate, attach to it, and then metamorphose into benthic adults. Anthropogenic ocean acidification (OA) is postulated to affect larval metamorphic success through an altered protein expression pattern (proteome structure) and post-translational modifications. To test this hypothesis, larvae of an economically and ecologically important barnacle species Balanus amphitrite, were cultured from nauplius to the cyprid stage in the present (control) and in the projected elevated concentrations of CO(2) for the year 2100 (the OA treatment). Cyprid response to OA was analyzed at the total proteome level as well as two protein post-translational modification (phosphorylation and glycosylation) levels using a 2-DE based proteomic approach. The cyprid proteome showed OA-driven changes. Proteins that were differentially up or down regulated by OA come from three major groups, namely those related to energy-metabolism, respiration, and molecular chaperones, illustrating a potential strategy that the barnacle larvae may employ to tolerate OA stress. The differentially expressed proteins were tentatively identified as OA-responsive, effectively creating unique protein expression signatures for OA scenario of 2100. This study showed the promise of using a sentinel and non-model species to examine the impact of OA at the proteome level.
Differential Diagnosis of Breast Cancer Using Quantitative, Label-free and Molecular Vibrational Imaging
Biomedical Optics Express. Aug, 2011 | Pubmed ID: 21833355
We present a label-free, chemically-selective, quantitative imaging strategy to identify breast cancer and differentiate its subtypes using coherent anti-Stokes Raman scattering (CARS) microscopy. Human normal breast tissue, benign proliferative, as well as in situ and invasive carcinomas, were imaged ex vivo. Simply by visualizing cellular and tissue features appearing on CARS images, cancerous lesions can be readily separated from normal tissue and benign proliferative lesion. To further distinguish cancer subtypes, quantitative disease-related features, describing the geometry and distribution of cancer cell nuclei, were extracted and applied to a computerized classification system. The results show that in situ carcinoma was successfully distinguished from invasive carcinoma, while invasive ductal carcinoma (IDC) and invasive lobular carcinoma were also distinguished from each other. Furthermore, 80% of intermediate-grade IDC and 85% of high-grade IDC were correctly distinguished from each other. The proposed quantitative CARS imaging method has the potential to enable rapid diagnosis of breast cancer.
Motion Correction for Cellular-resolution Multi-photon Fluorescence Microscopy Imaging of Awake Head-restrained Mice Using Speed Embedded HMM
Computerized Medical Imaging and Graphics : the Official Journal of the Computerized Medical Imaging Society. Sep, 2011 | Pubmed ID: 21890321
Multi-photon fluorescence microscopy (MFM) captures high-resolution fluorescence image sequences and can be used for the intact brain imaging of small animals. Recently, it has been extended from anesthetized and head-stabilized mice to awake and head-restrained ones for in vivo neurological study. In these applications, motion correction is an important pre-processing step since brain pulsation and body movement can cause motion artifact and prevent stable serial image acquisition at such high spatial resolution. This paper proposes a speed embedded Hidden Markov model (SEHMM) for motion correction in MFM imaging of awake head-restrained mice. The algorithm extends the traditional Hidden Markov model (HMM) method by embedding a motion prediction model to better estimate the state transition probability. The novelty of the method lies in using adaptive probability to estimate the linear motion, while the state-of-the-art method assumes that the highest probability is assigned to the case with no motion. In experiments we demonstrated that SEHMM is more accurate than the traditional HMM using both simulated and real MFM image sequences.
On-the-spot Lung Cancer Differential Diagnosis by Label-free, Molecular Vibrational Imaging and Knowledge-based Classification
Journal of Biomedical Optics. Sep, 2011 | Pubmed ID: 21950918
We report the development and application of a knowledge-based coherent anti-Stokes Raman scattering (CARS) microscopy system for label-free imaging, pattern recognition, and classification of cells and tissue structures for differentiating lung cancer from non-neoplastic lung tissues and identifying lung cancer subtypes. A total of 1014 CARS images were acquired from 92 fresh frozen lung tissue samples. The established pathological workup and diagnostic cellular were used as prior knowledge for establishment of a knowledge-based CARS system using a machine learning approach. This system functions to separate normal, non-neoplastic, and subtypes of lung cancer tissues based on extracted quantitative features describing fibrils and cell morphology. The knowledge-based CARS system showed the ability to distinguish lung cancer from normal and non-neoplastic lung tissue with 91% sensitivity and 92% specificity. Small cell carcinomas were distinguished from nonsmall cell carcinomas with 100% sensitivity and specificity. As an adjunct to submitting tissue samples to routine pathology, our novel system recognizes the patterns of fibril and cell morphology, enabling medical practitioners to perform differential diagnosis of lung lesions in mere minutes. The demonstration of the strategy is also a necessary step toward in vivo point-of-care diagnosis of precancerous and cancerous lung lesions with a fiber-based CARS microendoscope.
Cortical and Frontal Atrophy Are Associated with Cognitive Impairment in Age-related Confluent White-matter Lesion
Journal of Neurology, Neurosurgery, and Psychiatry. Jan, 2011 | Pubmed ID: 20826875
Although age-related confluent white-matter lesion (WML) is an important substrate for cognitive impairment, the mechanisms whereby WML induces cognitive impairment are uncertain. The authors investigated cognitive predictors in patients with confluent WML.
