Exogenous Contrast Agents Research Articles

Deep Learning‐Based Optical‐Resolution Photoacoustic Microscopy for In Vivo 3D Microvasculature Imaging and Segmentation

Optical‐resolution photoacoustic microscopy (OR‐PAM) technique is a noninvasive imaging technique that can be used to obtain high‐resolution images. This technique does not require the use of exogenous contrast agents. The technique can be effectively used to realize endogenous and exogenous imaging of microvasculature. However, the depth of focus (DOF) realized using OR‐PAM is low and inadequate to cover the entire 3D data for microvasculature imaging. A varying extent of signal‐to‐noise ratio (SNR) is recorded when varying depths of the 3D sample are studied. This significantly hindered the processes of image recognition, segmentation, and analysis. Herein, a deep learning‐based OR‐PAM technique to image and analyze 3D datasets is proposed. Endogenous and exogenous multi‐organ imaging data are sequentially imaged and segmented, and excellent generalization ability is observed. Wide‐field and ultradense exogenous 3D imaging of mouse brain vasculature located at different depths is obtained and segmented by OR‐PAM for the first time. The results reveal that the proposed method can be used for effectively imaging the entire microvasculature. The method can be potentially used for imaging the microcirculation system in clinics.

State of the Art in Carbon Nanomaterials for Photoacoustic Imaging.

Photoacoustic imaging using energy conversion from light to ultrasound waves has been developed as a powerful tool to investigate in vivo phenomena due to their complex characteristics. In photoacoustic imaging, endogenous chromophores such as oxygenated hemoglobin, deoxygenated hemoglobin, melanin, and lipid provide useful biomedical information at the molecular level. However, these intrinsic absorbers show strong absorbance only in visible or infrared optical windows and have limited light transmission, making them difficult to apply for clinical translation. Therefore, the development of novel exogenous contrast agents capable of increasing imaging depth while ensuring strong light absorption is required. We report here the application of carbon nanomaterials that exhibit unique physical, mechanical, and electrochemical properties as imaging probes in photoacoustic imaging. Classified into specific structures, carbon nanomaterials are synthesized with different substances according to the imaging purposes to modulate the absorption spectra and highly enhance photoacoustic signals. In addition, functional drugs can be loaded into the carbon nanomaterials composite, and effective in vivo monitoring and photothermal therapy can be performed with cell-specific targeting. Diverse applied cases suggest the high potential of carbon nanomaterial-based photoacoustic imaging in in vivo monitoring for clinical research.

Gene reporters for magnetic resonance imaging

MRI-based gene reporters allow imaging of gene expression at depth (tens of centimetres) and at relatively high resolution (~10-100 μm) and have the potential to be translated to the clinic. The reporters exploit either endogenous contrast mechanisms or they modulate the response to an introduced exogenous contrast agent.

Detection of tumour boundary in metastatic liver disease with 2D multibreath-hold susceptibility-weighted imaging

PurposeTo investigate the feasibility of susceptibility weighted imaging (SWI) in detecting tumour boundaries in metastatic liver disease (MLD) without contrast agent, and whether SWI can provide pathophysiologic information for preoperative evaluation. MethodsThirty patients with MLD underwent tumour resection. All patients underwent conventional MRI (T1-weighted and T2-weighted imaging), contrast-enhanced (CE) MRI and multibreath-hold 2D SWI. The conspicuity of the tumour boundary was assessed using a 4-grade scale. The detection rate of tumour boundaries and areas were reviewed and measured. The longest dimension was used to estimate the tumour size from the MR image. The conspicuity of the tumour boundary and area were compared using a nonparametric multi-group comparison (Friedman M). The McNemar test was applied to examine differences in the detection rate of tumour boundaries. ResultsAmong four different MRI sequences, SWI exhibited increased conspicuity of the tumour boundary than the conventional MRI (P < 0.001). SWI (91.8%) and CE-MRI (64.4%) exhibited higher detection rates of the tumour boundary than T1WI and T2WI (6.8% and 12.3% respectively). Longer tumour maximum diameters were measured with SWI (29.1 ± 17.2 mm) and CE-MRI (28.2 ± 16.8) compared to conventional MRI (P < 0.05). Conclusion2D multibreath-hold SWI enables enhanced noninvasive detection of tumour boundaries in patients with MLD compared with conventional MRI and CE-MRI without using an exogenous contrast agent. SWI has the potential to become a preoperative assessment standard that complements conventional MRI.

Phosphate buffer-catalyzed kinetics of mutarotation of glucosamine investigated by NMR spectroscopy

Glucosamine (2-amino-2-deoxy-d-glucose, GlcN) is a naturally occurring amino monosaccharide that is essential for a variety of biological functions, it is mainly involved in the formation of polysaccharide structures. It was recently reported to enable the imaging of cancerous tumors as an exogenous contrast agent using the MRI technique of chemical exchange saturation transfer (CEST). In preparation for the clinical use of GlcN, its anomeric equilibrium and mutarotation rate constants were directly investigated in this study utilizing high resolution 1H and 13C NMR spectroscopy. The effects of GlcN concentration, temperature, pH and buffer on the mutarotation rate constant and mutarotation equilibrium were measured. The mutarotation rate constant increased markedly with increasing GlcN concentrations. The rate constant of mutarotation of GlcN at room temperature was 2.2 × 10−4 - 5.0 × 10−4 s−1 at concentrations of 0.02–0.5 M, corresponding to a time of 3.8–1.7 h to reach 95% equilibrium. The anomeric ratio was strongly pH-dependent. The influence of phosphate buffer on the apparent rate constant of GlcN mutarotation was investigated. For phosphate buffer saline values between 0 and 50 mM, there was a six-fold increase in rate at pH 7.0. The mutarotation rate constant rose rapidly with pH at a phosphate concentration of 50 mM: from 0.4 × 10−3 s−1 at pH 5.0 to 7.8 × 10−3 s−1 at pH 9.4, suggesting that the catalysis is due to the HPO42− and PO43− ions. These findings might help researchers design the experimental setting for employing GlcN for cancer detection using GlcN-CEST MRI.

Multiscale confocal photoacoustic dermoscopy to evaluate skin health.

Photoacoustic dermoscopy (PAD) is a promising branch of photoacoustic microscopy (PAM) that can provide a range of functional and morphologic information for clinical assessment and diagnosis of dermatological conditions. However, most PAM setups are unsuitable for clinical dermatology because their single-scale mode and narrow frequency band result in insufficient imaging depth or poor spatiotemporal resolution when visualizing the internal texture of the skin. We developed a multiscale confocal photoacoustic dermoscopy (MC-PAD) with a multifunction opto-sono objective that could achieve high quality dermatological imaging. Using the objective to coordinate the spatial resolution and penetration depth, the MC-PAD was used to visualize pathophysiological biomarkers and vascular morphology from the epidermis (EP) to the dermis, which enabled us to quantify skin abnormalities without using exogenous contrast agents for human skin. The MC-PAD was shown to have the ability to differentiate between different types of cells (such as red blood cells and melanoma cells), image and quantify pigment of the skin, and visualize skin morphology and blood capillary landmarks. The MC-PAD detected a significant difference in the structures of some pigmented and vascular lesions of skin diseases compared with that of healthy skin (P<0.01). The café au lait macule (CALM) skin type was found to have a relatively higher melanin concentration and thicker stratum basale (SB) in the EP than healthy skin. The dermal vascular network of skin that had a port wine stain (PWS) had greater diameters and a denser distribution than healthy skin, as reported in clinical trials. The MC-PAD has a broad range of applications for the diagnosis of human skin diseases and evaluation of the curative effect of treatments, and it can offer new perspectives in biomedical sciences.

Angiopep-2 as an Exogenous Chemical Exchange Saturation Transfer Contrast Agent in Diagnosis of Alzheimer's Disease.

Background Chemical exchange saturation transfer (CEST) is a novel imaging modality in clinical practice and scientific research. Angiopep-2 is an artificial peptide that can penetrate blood-brain barrier. The aim of this study was to explore the feasibility of Angiopep-2 serving as an exogenous CEST contrast. Methods Phantoms of Angiopep-2 with different concentrations were prepared and then scanned using the 7.0T small animal MRI scanner. Different parameters including saturation powers and saturation duration were used to achieve the optimal CEST effect, and the optimal parameters were finally selected based on Z-spectra, asymmetric spectra, and phantom CEST imaging. CEST scanning of dimethyl sulfoxide (DMSO), the substance helping Angiopep-2 to be dissolved in water, was performed to exclude its contribution for the CEST effect. Results A broad dip was observed from 2.5 to 3.5 ppm in the Z-spectra of Angiopep-2 phantoms. The most robust CEST was generated at 3.2 ppm when using formula (M–3.2ppm − M+3.2ppm)/M–3.2ppm. The CEST effect of Angiopep-2 was concentration dependent; the effect increased as the concentration increased. In addition, the CEST effect was more obvious as the saturation power increased and peaked at 5.5 µT, and the CEST effect increased as the saturation duration increased. DMSO showed nearly 0% of the CEST effect at 3.2 ppm. Conclusions Our results demonstrate that Angiopep-2 can act as an excellent exogenous CEST contrast. As it can penetrate blood-brain barrier and bind amyloid-β protein, amyloid-β targeting CEST, with Angiopep-2 as an exogenous contrast agent, can be potentially used as a novel imaging modality for early diagnosis of Alzheimer's disease. Collectively, Angiopep-2 may play a critical role in early diagnosis of Alzheimer's disease.

Role of Magnetic Resonance Perfusion Imaging in Acute Stroke: Arterial Spin Labeling Versus Dynamic Susceptibility Contrast-Enhanced Perfusion.

Introduction: The role of perfusion neuroimaging in managing cases of acute ischemic stroke (AIS) is to identify ischemic penumbra and regions of hypo-perfusion, which can be salvaged. Dynamic susceptibility contrast (DSC) perfusion imaging techniques have been the main magnetic resonance imaging (MRI) perfusion techniques used to identify AIS. Arterial spin labelling (ASL) is an alternative non-invasive perfusion technique, which permits tissue perfusion measurement without any need for administration of exogenous contrast agents. The objective was to compare the diagnostic accuracy of ASL perfusion MRI versus DSC enhanced perfusion MRI in detecting perfusion-diffusion mismatch of varying volumes in acute ischemic stroke.Materials and methods: A hospital-based observational cross-sectional study was done in a tertiary care institute in Tamil Nadu between December 2018 to October 2019. Fifty-five subjects aged more than 18 years referred to the Radio-diagnosis department (less than 24 hours since the onset of weakness) for emergency assessment of suspected acute stroke were subjected to MRI stroke scan protocol. Then AIS cases were evaluated with ASL and DSC perfusion-weighted imaging. The collected data was entered in Excel (Microsoft, Redmond, WA, USA). IBM SPSS version 22 (IBM Corp., Armonk, NY, USA) was used for statistical analysis. Receiver operating characteristic (ROC) analysis was done to assess the predictive validity of ASL in predicting DSC mismatch. The diagnostic accuracy of ASL was the primary outcome variable. P-value < 0.05 was considered statistically significant.Results: Forty-four subjects confirmed as stroke were included in the final analysis. Their mean (±SD) age was 53.84 (±10.80) years. 72.7% were males. The majority (53.8%) presented during the acute stage of cerebral infarction (53.8%). The majority (45.5%) had hemiplegia followed by aphasia (27.3%). The major vascular territory involved was the middle cerebral artery (54.5%). The sensitivity, specificity, positive predictive value, and negative predictive value of ASL (non-contrast) in predicting DSC (contrast) mismatch was found to be 71.43%, 78.57%, 83.33%, and 64.71% respectively.Conclusion: ASL MR has the potential to replace MRI DSC perfusion in the future imaging diagnostic work-up for stroke. However, further studies are required to validate its role as the first-line imaging for stroke therapy.

How Could Nanomedicine Improve the Safety of Contrast Agents for MRI during Pregnancy?

Pregnancy is a delicate state, during which timely investigation of possible physiological anomalies is essential to reduce the risk of maternal and fetal complications. Medical imaging encompasses different technologies to image the human body for the diagnosis, course of treatment management, and follow-up of diseases. Ultrasound (US) is currently the imaging system of choice for pregnant patients. However, sonographic evaluations can be non-effective or give ambiguous results. Therefore, magnetic resonance imaging (MRI), due to its excellent tissue penetration, the possibility of acquisition of three-dimensional anatomical information, and its high spatial resolution, is considered a valid diagnostical alternative. Nevertheless, currently employed contrast agents to improve the MRI image quality are harmful to the fetus. Because of their ability to cross the placenta, their use on pregnant patients is avoided. This review will firstly recapitulate the most common non-obstetrical, obstetrical, and fetal indications for magnetic resonance imaging on pregnant women. Fetal safety risks, due to the use of strong magnetic fields and exogenous contrast agents, will be presented. Then, possible advantages of nanostructured contrast agents compared to current molecular ones are explored. Nanosystems’ characteristics affecting contrast efficiency, and their potential for improving contrast-enhanced MRI’s safety in pregnant women, are discussed. Lastly, promising examples of nanoparticles as safer alternatives to current MRI contrast agents in pregnancy are discussed.

Reversibly Photoswitching Upconversion Nanoparticles for Super‐Sensitive Photoacoustic Molecular Imaging

AbstractPhotoacoustic (PA) imaging uses light excitation to generate the acoustic signal for detection and improves tissue penetration depth and spatial resolution in the clinically relevant depth of living subjects. However, strong background signals from blood and pigments have significantly compromised the sensitivity of PA imaging with exogenous contrast agents. Here we report a nanoparticle‐based probe design that uses light to reversibly modulate the PA emission to enable photoacoustic photoswitching imaging (PAPSI) in living mice. Such a nanoprobe is built with upconverting nanocrystals and photoswitchable small molecules and can be switched on by NIR light through upconversion to UV energy. Reversibly photoswitching of the nanoprobe reliably removed strong tissue background, increased the contrast‐to‐noise ratio, and thus improved imaging sensitivity. We have shown that PAPSI can image 0.05 nM of the nanoprobe in hemoglobin solutions and 104 labeled cancer cells after implantation in living mice using a commercial PA imager.

Relaxation-Compensated Chemical Exchange Saturation Transfer MRI in the Brain at 7T: Application in Relapsing-Remitting Multiple Sclerosis.

Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) can probe tissue biochemistry in vivo with high resolution and sensitivity without requiring exogenous contrast agents. Applying CEST MRI at ultrahigh field provides advantages of increasing spectral resolution and improving sensitivity to metabolites with faster proton exchange rates such as glutamate, a critical neurotransmitter in the brain. Prior magnetic resonance spectroscopy and CEST MRI studies have revealed altered regulation of glutamate in patients with multiple sclerosis (MS). While CEST imaging facilitates new strategies for investigating the pathology underlying this complex and heterogeneous neurological disease, CEST signals are contaminated or diluted by concurrent effects (e.g., semi-solid magnetization transfer (MT) and direct water saturation) and are scaled by the T1 relaxation time of the free water pool which may also be altered in the context of disease. In this study of 20 relapsing-remitting MS patients and age- and sex-matched healthy volunteers, glutamate-weighted CEST data were acquired at 7.0 T. A Lorentzian fitting procedure was used to remove the asymmetric MT contribution from CEST z-spectra, and the apparent exchange-dependent relaxation (AREX) correction was applied using an R1 map derived from an inversion recovery sequence to further isolate glutamate-weighted CEST signals from concurrent effects. Associations between AREX and cognitive function were examined using the Minimal Assessment of Cognitive Function in MS battery. After isolating CEST effects from MT, direct water saturation, and T1 effects, glutamate-weighted AREX contrast remained higher in gray matter than in white matter, though the difference between these tissues decreased. Glutamate-weighted AREX in normal-appearing gray and white matter in MS patients did not differ from healthy gray and white matter but was significantly elevated in white matter lesions. AREX in some cortical regions and in white matter lesions correlated with disability and measures of cognitive function in MS patients. However, further studies with larger sample sizes are needed to confirm these relationships due to potential confounding effects. The application of MT and AREX corrections in this study demonstrates the importance of isolating CEST signals for more specific characterization of the contribution of metabolic changes to tissue pathology and symptoms in MS.

Benzobisthiadiazole and Its Derivative-Based Semiconducting Polymer Nanoparticles for Second Near-Infrared Photoacoustic Imaging.

Photoacoustic (PA) imaging has received more and more attention on disease diagnosis and fundamental scientific research. It is still challenging to amplify their imaging ability and reduce the toxicity of inorganic materials and exogenous contrast agents. Semiconducting polymer nanoparticles (SPNs), as a new type of contrast agent, have the advantages of low toxicity, flexible structure adjustment, good photostability, and excellent photothermal conversion efficiency. SPNs containing benzo(1,2-c;4,5-c′)bis(1,2,5)thiadiazole (BBT) units, as the most classic second near-infrared window (NIR-II, 1,000–1700 nm) PA contrast agents, can achieve light absorption in the NIR-II region, thereby effectively reducing light loss in biological tissues and improving imaging resolution. This mini review summarizes the recent advances in the design strategy of BBT and its derivative-based semiconducting polymer nanoparticles for second near-infrared photoacoustic imaging. The evolution process of BBT blocks provides a unique perspective for the design of high-performance NIR-II PA contrast agents.

Reversibly Photoswitching Upconversion Nanoparticles for Super-Sensitive Photoacoustic Molecular Imaging.

Photoacoustic (PA) imaging uses light excitation to generate the acoustic signal for detection and improves tissue penetration depth and spatial resolution in the clinically relevant depth of living subjects. However, strong background signals from blood and pigments have significantly compromised the sensitivity of PA imaging with exogenous contrast agents. Here we report a nanoparticle-based probe design that uses light to reversibly modulate the PA emission to enable photoacoustic photoswitching imaging (PAPSI) in living mice. Such a nanoprobe is built with upconverting nanocrystals and photoswitchable small molecules and can be switched on by NIR light through upconversion to UV energy. Reversibly photoswitching of the nanoprobe reliably removed strong tissue background, increased the contrast-to-noise ratio, and thus improved imaging sensitivity. We have shown that PAPSI can image 0.05 nM of the nanoprobe in hemoglobin solutions and 104 labeled cancer cells after implantation in living mice using a commercial PA imager.

Visualization of blood-brain barrier disruption with dual-wavelength high-resolution photoacoustic microscopy.

The blood-brain barrier (BBB) strictly regulates the substance exchange between the vascular network and the central nervous system, and plays a critical role in maintaining normal brain homeostasis. Impaired BBB is often accompanied with the emergence of cerebral diseases and probably further leads to severe neuroinflammation or even neurological degeneration. Hence, there is an urgent need to precisely monitor the impaired BBB to understand its pathogenesis and better guide the enactment of therapeutic strategies. However, there is a lack of high-resolution imaging techniques to visualize and evaluate the large-scale BBB disruption in pre-clinical and clinical aspects. In this study, we propose a dual-wavelength photoacoustic imaging (PAI) methodology that simultaneously reveals the abnormal microvasculature and impaired BBB within the cerebral cortex. In in vivo studies, BBB disruption in both mice and rats were induced by local hot-water stimulation and unilateral carotid arterial perfusion of hyperosmolar mannitol, respectively. Subsequently, the exogenous contrast agent (CA) was injected into the microcirculation via the tail vein, and photoacoustic (PA) images of the microvasculature and leaked CA within the cerebral cortex were obtained by dual-wavelength photoacoustic microscopy to evaluate the BBB disruption. Besides, analysis of distribution and concentration of leaked CA in lesion region was further conducted to quantitatively reveal the dynamic changes of BBB permeability. Furthermore, we exploited this approach to investigate the reversibility of BBB disruption within the two distinct models. Based on the experimental results, this new proposed approach presents excellent performance in visualizing microvasculature and leaked CA, and enabling it possesses great potential in evaluating the abnormal microvasculature and impaired BBB result from cerebrovascular diseases.

Vmeasur: A software package for experimental and clinical measurement of mesenteric lymphatic contractile function over an extended vessel length.

Conventionally, in vivo mesenteric lymphatic contractile function is measured using a high magnification transmission microscope (field of view 0.3-1.5mm), which precludes visualization of extended lengths of vessels embedded in mesenteric fat. Existing software is not optimized for imaging at a low magnification using a contrast agent. We aimed to develop a simple and clinically transferable method for in situ visualization, image analysis, and quantitative assessment of mesenteric lymphatic contractile function over an extended area. Subserosal injection of various blue dyes was taken up by mesenteric lymphatics and visualized under a stereomicroscope (25×), allowing for video recording of 1.4×1.1cm of intact mesentery. A new R package ("vmeasur") that combines multiple high-performance image analyses into a single workflow was developed. The edges of each vessel were determined by applying an automated threshold to each frame (with real-time manual verification). The vessel width at every point in each frame was plotted to provide contractile parameters over time and along the lymphatic vessel length. Contractile parameters and their differences along the length of the vessel were accurately calculated in a rodent model. In a human mesenteric lymphatic, the algorithm was also able to measure changes in diameter over length. This software offers a low cost, rapid, and accessible method to measure lymphatic contractile function over a wide area, showing differences in contractility along the length of a vessel. Because the presence of mesenteric fat has less of an impact on imaging, due to the use of an exogenous contrast agent, there is potential for clinical application.

Exogenous Contrast Agents in Photoacoustic Imaging: An In Vivo Review for Tumor Imaging.

The field of cancer theranostics has grown rapidly in the past decade and innovative ‘biosmart’ theranostic materials are being synthesized and studied to combat the fast growth of cancer metastases. While current state-of-the-art oncology imaging techniques have decreased mortality rates, patients still face a diminished quality of life due to treatment. Therefore, improved diagnostics are needed to define in vivo tumor growths on a molecular level to achieve image-guided therapies and tailored dosage needs. This review summarizes in vivo studies that utilize contrast agents within the field of photoacoustic imaging—a relatively new imaging modality—for tumor detection, with a special focus on imaging and transducer parameters. This paper also details the different types of contrast agents used in this novel diagnostic field, i.e., organic-based, metal/inorganic-based, and dye-based contrast agents. We conclude this review by discussing the challenges and future direction of photoacoustic imaging.

Photoacoustic response optimization of gold nanorods in the near-infrared region

Photoacoustic imaging (PAI) combines the advantage of optical and ultrasonic imaging, which has a high signal-to-noise ratio, and spatial resolution. To further improve the performance of PAI, gold nanorods can be utilized as exogenous contrast agents, and their size can be controlled. The size change of gold nanorods will change their absorption and heat transfer characteristics, and then affect their photoacoustic characteristics. Therefore, in the present work, the influences of absorption characteristics (absorption cross section and volume absorption coefficient) and heat transfer characteristics (specific surface area) of gold nanorods on photoacoustic response are studied by FDTD (FDTD Solutions, Lumerical) and FEM (Comsol Multiphysics). Results show that the increase of specific surface area will enhance the thermal coupling between gold nanorods and water, so as to improve the heat transfer and produce different photothermal responses without significantly affecting the photoacoustic quantum yield (As the specific surface area increases by about 10 times, the temperature increases by about 12 times, while the photoacoustic quantum yield increases by about 24%). On the contrary, absorption characteristics are decisive factors for both photothermal and photoacoustic responses. Therefore, in terms of improving photoacoustic quantum yield, when the size of gold nanorods changes, more attention should be paid to the improvement of the absorption characteristics rather than the specific surface area. In addition, increasing the specific surface area can significantly improve the photostability of gold nanorods, which is very important for practical applications.

Near-infrared active superparamagnetic iron oxide nanoparticles for magnetomotive optical coherence tomography imaging and magnetic hyperthermia therapeutic applications

A green chemistry-based approach to nanoparticle synthesis is an eco-friendly, simple, and cost-effective way to fabricate nanoparticles. This study aims at the biomedical applications of green synthesized near-infrared (NIR) active superparamagnetic iron oxide nanoparticles (SPIONs). The SPIONs obtained by the green synthesis route are non-toxic and their surface is free from any chemical impurity. The MTT [3-(4, 5-Dimethylthiazol-2-yl)-2, 5-Diphenyltetrazolium Bromide] assay was accomplished on human cervical cancer (HeLa) cells and shows that the SPIONs are biocompatible and thus safe for cells even at higher concentrations up to 500 μg/ml. The synthesized SPIONs display an absorbance in the tissue transparent NIR wavelength region. The SPIONs exhibit a superparamagnetic behavior with high saturation magnetization of 66 emu/g. Owing to their excellent optical and magnetic properties, the potential of these green synthesized SPIONs as an exogenous contrast agent in deep-tissue magnetomotive optical coherence tomography (MM-OCT) imaging was evaluated ex-vivo using chicken breast tissue. A significant enhancement in the contrast and the penetration depth was observed with time. The heating response of green synthesized SPIONs was evaluated under the application of an external magnetic field. The results suggest that these SPIONs could be used as theranostic agents for deep tissue biomedical imaging and therapeutic applications.

Qualitative Assessment of Cerebral Perfusion in Post Stroke Seizure Patients using Arterial Spin Labeling: A Case-control Study

Introduction: Arterial Spin Labeling-Perfusion Weighted Imaging (ASL-PWI) assesses cerebral blood flow using magnetically labeled inflowing arterial blood water protons as freely diffusible tracer without exogenous contrast agent. Seizures are one of the sequelae of stroke with its mechanism not well studied. Aim: Qualitative assessment of cerebral perfusion in post stroke seizure patients using ASL-PWI and comparison of perfusion patterns in post stroke seizure patients and stroke patients. Materials and Methods: This was a case-control study among 100 stroke patients who underwent Magnetic Resonance Imaging (MRI) of brain in Department of Radiodiagnosis, from Outpatient and Inpatient Department of Neurology, Christian Medical College, Ludhiana, Punjab, India, from 1st January 2018 till 1st January 2020. Total 50 post stroke seizure patients included as cases and 50 age matched post stroke patients without seizure included as controls. Perfusion pattern was compared qualitatively using ASL-PWI. Qualitative variables were associated using Chi-square test/Fisher’s-exact test. Results: The mean age of the study subjects were 56.38±16.98 years (age range from 19-87 years) and that of controls were 59.66±11.86 years (age range from 19-89 years) (p-value=0.265). Cerebral hypoperfusion was noted in 39 (78%) of total 50 post stroke seizure patients irrespective of type of stroke. Cortical and subcortical area of frontal and parietal lobes was predominantly involved in post stroke seizure patients. Out of 39, 23 (71.88%) early onset seizure and 16 (88.89%) late onset seizure patients had hypoperfusion. There was no significant association of perfusion abnormality with onset of seizure (p-value=0.241). Hypoperfusion was noted in cases and controls without any statistical difference. Conclusion: Cortical and subcortical area of involvement was noted in post stroke seizure patients. Post stroke seizure patients showed hypoperfusion irrespective of stroke type and onset of seizure. There was no difference seen in perfusion abnormality between post stroke seizure patients and stroke patients without seizure.

Functional imaging of human retina using integrated multispectral and laser speckle contrast imaging.

A novel integration of retinal multispectral imaging (MSI), retinal oximetry and laser speckle contrast imaging (LSCI) is presented for functional imaging of retinal blood vessels that could potentially allow early detection or monitoring of functional changes. We designed and built a cost-effective, scalable, retinal imaging instrument that integrates structural and functional retinal imaging techniques, including MSI, retinal oximetry and LSCI. Color fundus imaging was performed with 470 nm, 550 nm and 600 nm wavelength light emitting diode (LED) illumination. Retinal oximetry was performed using 550 nm and 600 nm LED illumination. LSCI of blood flow was performed using 850 nm laser diode illumination at 82 frames per second. LSCI can visualize retinal and choroidal vasculature without requiring exogenous contrast agents and can provide time-resolved information on blood flow, generating a cardiac pulse waveform from retinal vasculature. The technology can rapidly acquire structural MSI images, retinal oximetry and LSCI blood flow information in a simplified clinical workflow without requiring patients to move between instruments. Results from multiple modalities can be combined and registered to provide structural as well as functional information on the retina. These advances can reduce barriers for clinical adoption, accelerating research using MSI, retinal oximetry and LSCI of blood flow for diagnosis, monitoring and elucidating disease pathogenesis.