Multi-channel delay sampling to extend imaging depth in high-speed swept-source OCT systems.

We present a multi-channel delay sampling method to extend imaging depth in high-speed swept-source optical coherence tomography (SS-OCT). A balanced detector captures interference signals, converting them into electrical signals, which are then split into N channels, each with fixed time delays determined by the length of electrical cables. Then, they are digitized by an N-channel acquisition card. A calibration procedure is utilized to compensate for non-uniform phase shifts resulting from fixed time delays. The N-channel signals are merged in k-space and resampled to obtain a linearized spectrum, which increases the sampling rate by a factor of N, thereby extending the ranging distance by N times, all without altering k-clock triggering or sacrificing other imaging performance. The signal-to-noise ratio and sensitivity within the original depth range also have been enhanced. This advancement contributes to the improvement of the overall performance of SS-OCT systems.

Retinal perfusion is linked to cognition and brain MRI biomarkers in Black Americans.

INTRODUCTION: We investigated whether retinal capillary perfusion is a biomarker of cerebral small vessel disease and impaired cognition among Black Americans, an understudied group at higher risk for dementia. METHODS: We enrolled 96 Black Americans without known cognitive impairment. Four retinal perfusion measures were derived using optical coherence tomography angiography. Neurocognitive assessment and brain magnetic resonance imaging (MRI) were performed. Multiple linear regression analyses were performed. RESULTS: Lower retinal capillary perfusion was correlated with worse Oral Symbol Digit Test (P < = 0.005) and Fluid Cognition Composite scores (P < = 0.02), but not with the Crystallized Cognition Composite score (P > = 0.41). Lower retinal perfusion was also correlated with higher free water and peak width of skeletonized mean diffusivity, and lower fractional anisotropy (all P < 0.05) on MRI (N = 35). DISCUSSION: Lower retinal capillary perfusion is associated with worse information processing, fluid cognition, and MRI biomarkers of cerebral small vessel disease, but is not related to crystallized cognition.

Sex Difference in Capillary Reperfusion After Transient Middle Cerebral Artery Occlusion in Diabetic Mice.

BACKGROUND: Type 2 diabetes (DM2) exacerbates stroke injury, reduces efficacy of endovascular therapy, and worsens long-term functional outcome. Sex differences exist in stroke incidence, response to therapy, poststroke microvascular dysfunction, and functional recovery. In this study, we tested the hypotheses that poor outcome after stroke in the setting of DM2 is linked to impaired microvascular tissue reperfusion and that male and female DM2 mice exhibit different microvascular reperfusion response after transient middle cerebral artery occlusion (MCAO). METHODS: Transient MCAO was induced for 60 minutes using an intraluminal filament in young adult DM2 and nondiabetic control male and female mice. Capillary flux in deep cortical layers was assessed using optical coherence tomography-based optical microangiography (OMAG), and associated regional brain infarct size was evaluated by hematoxylin and eosin staining. RESULTS: Compared to baseline, MCAO reduced absolute capillary red blood cell flux by 84% at 24 hours post-MCAO in male DM2 (P<0.001) but not male control mice. When normalized to pre-MCAO baseline, red blood cell flux 24 hours after stroke was 64% lower in male DM2 mice than male nondiabetic controls (P<0.01). In females, MCAO decreased capillary flux by 48% at 24 hours post-MCAO compared with baseline in DM2 (P<0.05) but not in control mice. Red blood cell flux of female DM2 mice did not differ from that of nondiabetic controls either before or 24 hours after MCAO. Furthermore, normalized capillary flux 24 hours after MCAO failed to differ between female DM2 mice and nondiabetic controls. Concomitantly, male but not female DM2 mice experienced 25% larger infarct in caudate-putamen versus respective nondiabetic controls (P<0.05). CONCLUSIONS: DM2 impairs capillary perfusion and exacerbates ischemic deep brain injury in male but not female young adult mice. Premenopausal females appear to be protected against DM2-related capillary dysfunction and brain injury.

Longitudinal quantification of choriocapillaris flow deficits in persistent placoid maculopathy: a case report.

BACKGROUND: Persistent placoid maculopathy (PPM) is a rare idiopathic chorioretinopathy characterized by choriocapillaris (CC) hypoperfusion. In a case of PPM, we quantified CC flow deficits (FDs) over time and observed an increase in CC perfusion as the visual acuity and outer photoreceptor anatomy improved. CASE PRESENTATION: A 58-year-old man was diagnosed with PPM in both eyes based on the patient's clinical presentation and imaging. He presented with sudden-onset central scotomas in both eyes for about two months. On referral, the best corrected visual acuity (BCVA) was 20/20 in the right eye and 20/100 in the left eye. Plaque-like yellowish macular lesions were observed bilaterally and autofluorescence imaging showed bilateral hyperautofluorescent lesions. Fluorescein angiography (FA) revealed early-phase hyper-fluorescent staining that intensified in the late phases, while indocyanine green angiography (ICGA) displayed persistent hypofluorescence in both eyes. Foveal centered swept source optical coherence tomography (SS-OCT) B-scans showed bilateral focal deposits on the level of retinal pigment epithelium (RPE) and disruption of outer photoreceptor bands. The CC FDs were quantified on SS-OCT angiography (SS-OCTA) images using a previously published algorithm that was validated. The CC FD% was 12.52% in the right eye and 14.64% in the left eye within a 5 mm circle centered on the fovea. After 5 months of steroid treatment, BCVA remained 20/20 in the right eye and improved to 20/25 in the left eye. On OCT imaging, the outer photoreceptor bands fully recovered in both eyes, while some focal deposits remained along the RPE in the left eye. The CC perfusion in both eyes improved, with CC FD% decreasing from 12.52% to 9.16% in the right eye and from 14.64% to 9.34% in the left eye. CONCLUSIONS: Significant impairment of macular CC perfusion was detected after the onset of PPM. Improvement in central macular CC perfusion corresponded with improvements in BCVA and outer retinal anatomy. Our findings suggest that imaging and quantification of CC FDs could serve as a valuable imaging strategy for diagnosing PPM and for following disease progression.

Imaging-photoplethysmography-guided optical microangiography.

We report a method to image facial cutaneous microvascular perfusion using wide-field imaging photoplethysmography (iPPG) and handheld swept-source optical coherence tomography (OCT). The iPPG system employs a 16-bit-depth camera to provide a 2D wide-field blood pulsation map that is then used as a positioning guidance for OCT imaging of cutaneous microvasculature. We show the results from iPPG and OCT to demonstrate the ability of guided imaging of cutaneous microvasculature, which is potentially useful for the assessment of skin conditions in dermatology and cosmetology.

De-aliased depth-range-extended optical coherence tomography based on dual under-sampling.

We demonstrate a dual under-sampling (DUS) method to achieve de-aliased and depth-range-extended optical coherence tomography (OCT) imaging. The spectral under-sampling can significantly reduce the data size but causes well-known aliasing artifacts. A change in the sampling frequency used to acquire the interference spectrum alters the aliasing period within the output window except for the true image; this feature is utilized to distinguish the true image from the aliasing artifacts. We demonstrate that with DUS, the data size is reduced to 37% at an extended depth range of 24 mm, over which the true depth can be precisely measured without ambiguity. This reduction in data size and precise measuring capability would be beneficial for reducing the acquisition time for OCT imaging in various biomedical and industrial applications.

LONGITUDINAL ANALYSIS OF DIABETIC CHOROIDOPATHY IN PROLIFERATIVE DIABETIC RETINOPATHY TREATED WITH PANRETINAL PHOTOCOAGULATION USING WIDEFIELD SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY.

PURPOSE: Widefield swept-source optical coherence tomography (OCT) imaging was used to characterize choroidal thickness and vascularity at baseline in proliferative diabetic retinopathy (PDR) and longitudinally after panretinal photocoagulation (PRP). METHODS: Patients with treatment-naive PDR were imaged at baseline and at 1 week, 1 month, and 3 months after PRP. Previously validated algorithms were used to calculate the mean choroidal thickness (MCT) and choroidal vascularity index (CVI) in 5 regions of 12 mm × 12 mm scans. RESULTS: Fourteen PDR eyes were included. Baseline MCT in PDR eyes did not differ significantly from normal eyes, but CVI measurements in PDR eyes were lower in all regions (P < 0.001-0.008). After PRP, MCT measurements in PDR eyes were significantly lower at 1 month and 3 months in all regions (P < 0.001-0.005) except the fovea (P = 0.074). However, CVI measurements did not change over time in any region after PRP. CONCLUSION: The choroid in PDR eyes has a smaller CVI than that in normal eyes. After PRP, the choroidal thickness decreases outside the fovea, but the CVI remains constant, which suggests that a relative decrease in choroidal vascularity persists. These widefield swept-source OCT results are consistent with choroidal alterations found in histopathological reports of diabetic choroidopathy.

CHANGE IN CHORIOCAPILLARIS FLOW DEFICITS WITHIN TEARS OF THE RETINAL PIGMENT EPITHELIUM IMAGED WITH SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: Choriocapillaris (CC) flow deficits (FDs) were measured in the areas exposed by tears of the retinal pigment epithelium (RPE) before and after their onset to determine their change over time. METHODS: Patients enrolled in a prospective, swept-source optical coherence tomography angiography (SS-OCTA) study were retrospectively reviewed for RPE tears, and scans were evaluated before and after RPE tear formation. Choriocapillaris flow deficits were measured within the bed of the tear and within a symmetric control region. RESULTS: Three patients with RPE tears were imaged before tear formation and for at least 16 months afterward. When the baseline and first posttear visit were compared, CC FDs decreased by 1.0% in the tear region and 1.7% in the control region ( P = 0.84). When the 16-month follow-up visits were compared with the first post-RPE tear visits, CC FDs decreased by 1.9% in tear regions and increased by 1.3% in control regions ( P = 0.37). CONCLUSION: No significant changes in CC FDs were observed before and after RPE tear formation and for 16 months afterward, suggesting that CC FDs can be reliably detected in the presence of an intact RPE and the absence of the RPE did not affect CC perfusion for at least 16 months.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY DETECTION OF BRUCH MEMBRANE AND CHORIOCAPILLARIS ABNORMALITIES IN SORSBY MACULAR DYSTROPHY.

PURPOSE: Swept-source optical coherence tomography angiography (SS-OCTA) was used to analyze Bruch membrane (BM) and choriocapillaris (CC) abnormalities in undiagnosed family members with Sorsby macular dystrophy (SMD). METHODS: In a family with SMD ( TIMP3 Tyr191Cys), SS-OCTA imaging was performed using the 6 × 6 mm scan patter and previously validated algorithms to detect abnormalities in BM and the CC, as well as the presence of reticular pseudodrusen and macular neovascularization. Genetic analyses were performed for TIMP3 mutations. RESULTS: Of eight family members, two were previously diagnosed with SMD and six were asymptomatic. SS-OCTA imaging of the 33-year-old proband revealed type 1 macular neovascularization in the left eye and bilateral reticular pseudodrusen, thickening of BM, CC thinning, and increases in CC flow deficits. A TIMP3 mutation was confirmed. His niece, despite having no clinical evidence of SMD, showed BM thickening and CC thinning on SS-OCTA. A TIMP3 mutation was confirmed. The proband's younger nephew and niece also carried the TIMP3 mutation without clinical evidence of SMD. Two additional members had normal examinations, unremarkable SS-OCTA findings, and no TIMP3 mutation. CONCLUSION: Swept-source optical coherence tomography angiography imaging can detect BM and CC abnormalities in vivo in subjects unaware of their TIMP3 status in a family with SMD.

A moderate dosage of coffee causes acute retinal capillary perfusion decrease in healthy young individuals.

AIM: Caffeinated beverages are very popular across populations and cultures, but quantitative evidence of the acute effects of moderate coffee doses on retinal perfusion is sparse and contradicting. Thus, the aim of this randomized, cross-over and parallel-group design study was to investigate whether moderate consumption of coffee alters macular retinal capillary perfusion in young healthy individuals. METHODS: Twenty-seven young healthy individuals were recruited for this study. Acute changes in retinal microvasculature were assessed using spectral-domain optical coherence tomography angiography (SD-OCTA) at baseline, 0.5 h, and 2 h after intake of coffee, or water. Meanwhile, cerebral blood flow (CBF) and retina-choroid blood flow were evaluated in a parallel-group design (4 participants each in coffee or water group) using magnetic resonance imaging (MRI) with pseudo-continuous arterial spin labeling sequences. RESULTS: Two hours after coffee intake, blood caffeine concentration increased from 0 to 5.05 ± 1.36 µg/mL. Coffee caused a significant decrease in retinal vessel diameter index (VDI) (19.05 ± 0.24 versus [vs] 19.13 ± 0.26; p < 0.001) and CBF in the frontal lobe (77.47 ± 15.21 mL/100 mL/min vs. 84.13 ± 15.55 mL/100 mL/min; p < 0.05) 2 h after intake. However, it significantly increased retina-choroid blood flow after 0.5 and 2 h (163.18 ± 61.07 mL/100 mL/min vs. 132.68 ± 70.47 mL/100 mL/min, p < 0.001, and 161.21 ± 47.95 vs. 132.68 ± 70.47; p < 0.001, respectively). CONCLUSION: This is the first study to demonstrate the acute effects of daily dose coffee consumption on retinal capillary perfusion using SD-OCTA combinate with blood flow MRI. The findings imply that although moderate coffee intake caused a significant increase in retina-choroid blood flow, there was a significant acute decrease both in macular retinal capillary perfusion and CBF.

Early Retinal Microvasculopathy in Prediabetic Patients and Correlated Factors.

INTRODUCTION: We aimed to detect early retinal microcirculation changes in prediabetic patients and investigate their correlation with clinical examinations. METHODS: Forty-seven prediabetic individuals, 29 controls, and 81 type 2 diabetic mellitus (T2DM) patients were enrolled in this study. A review of clinical data and spectral-domain optical coherence tomography angiography (SD-OCTA) parameters of macular vessel diameter (VD), foveal avascular zone (FAZ), and macular vessel area density (VAD) was performed. RESULTS: Levels of low-density lipoprotein cholesterol and triglycerides in prediabetes and T2DM groups were significantly higher than those in the control group. Urine microalbumin-to-creatinine ratio (ACR) was mildly and moderately increased in the prediabetes and T2DM groups, respectively. Estimated glomerular filtration rate of the three groups were within the normal range. SD-OCTA showed that VAD in the superficial macular area was decreased in the prediabetes group compared to the control group (p=0.01). The FAZ size, particularly in the deep layer, was expanded in the prediabetes group. In the deep retinal layer of the macular area, VD and FAZ size in the prediabetes group were larger than those in the control group. In the prediabetes group, the axial length was significantly correlated with macular VD and FAZ size (p<0.05), and ACR was correlated with FAZ size (p<0.05). Age had a negative correlation with VAD (p<0.01). ACR had a positive correlation with FAZ size (p<0.05). CONCLUSIONS: Enlargement and irregularity of the FAZ area, deep capillary dilation, and decrease in VAD occur in the retina of prediabetes patients with mild kidney function impairment.

The disposable bandage soft contact lenses therapy and anterior segment optical coherence tomography for management of ocular graft-versus-host disease.

PURPOSE: To identify the ocular surface changes of ocular graft-versus-host disease (GVHD) using anterior segment optical coherence tomography (AS-OCT) and examine the efficacy of disposable bandage soft contact lens (BSCL) treatment in ocular GVHD patients. METHODS: This study is a prospective, Phase II clinical trial. Nineteen patients diagnosed with chronic GVHD based on the NIH criteria and ocular symptoms of NIH eye score 2 or greater were enrolled. Disposable BSCL was applied to the GVHD-affected eyes with topical antibiotic coverage. Ocular exams, eye symptom surveys, and AS-OCT were performed with signed informed consent. Patients were followed for one to three months. RESULTS: Thirty-eight eyes of 19 patients with ocular GVHD underwent BSCL treatment in this study. AS-OCT scans were done in 14 out of 19 patients. The mean best-corrected visual acuity at enrollment, 2-week, and 4-week visits was 0.180, 0.128, and 0.163 logMAR, respectively. Twenty-four out of 25 eyes (96 %) that initially presented with conjunctival inflammation, twenty-three out of 30 eyes (76.7 %) that initially presented with punctate epithelial erosion, and 8 out of 15 (53.3 %) eyes that initially presented with filamentous keratopathy showed improvement after wearing BSCL for 2 to 4 weeks. AS-OCT revealed corneal epithelial irregularity, abnormal meibomian gland orifice, and conjunctival hyperemia, in patients with ocular GVHD. CONCLUSIONS: BSCL treatment provided significant subjective and objective improvements in ocular GVHD patients. Meanwhile, we found that AS-OCT can be a promising diagnostic tool to characterize the ocular surface changes associated with ocular GVHD.

OCT-Based Angiography and Surface Topography in Burn-Damaged Skin.

BACKGROUND AND OBJECTIVES: There is a clinical need for an accurate, non-invasive imaging tool that can provide the objective assessment of burn wounds. The aims of this study are to demonstrate the potential of optical coherence tomography (OCT) in evaluating burn wound healing, as well as exploring the physiological basis of human wound healing. STUDY DESIGN/MATERIALS AND METHODS: This was a retrospective study. Seven patients with severe burn wounds who were admitted to Harborview Medical Center were imaged using an in-house-built, clinical-prototype OCT system. OCT imaging was carried out at multiple scan sites on the burned skin across two time points (imaging session #1 and #2) with a field of view of ~9 × 9 mm. Due to pathological differences among burn zones, scan sites were classified into red sites (zone of hyperemia), white sites (zone of coagulation), and mixed sites. In addition to obtaining qualitative en face vascular and surface topography maps, we quantified vascular area density and surface roughness for comparative purposes. RESULTS: En face vascular and surface topography maps demonstrated numerous morphological changes over both imaging sessions associated with burn injury, such as altered blood flow and loss of regular texture. Quantitative analyses revealed that during imaging session #1, vascular area density was significantly increased within the red sites compared with that of a healthy control (P = 0.0130), while vascular area density was significantly decreased within the white sites compared with that of a healthy control (P < 0.0001). During imaging session #2, vascular area density was significantly reduced to a more normal range within the red sites compared with imaging session #1 (P = 0.0215); however, vascular area density was still significantly lower within the white sites compared with that of a healthy control (P < 0.0001). Furthermore, vascular area density and surface roughness were significantly increased within the white sites during imaging session #2 compared with imaging session #1 (both P < 0.0001). CONCLUSIONS: OCT is clinically feasible to monitor vascular changes and alterations in skin surface roughness during the process of burn wound healing. Variations in vascular area density and roughness measurements within the burn wounds revealed by OCT offer some key insights into the underlying pathophysiological mechanisms responsible for wound healing, which may become critical biological indicators in future clinical evaluation and monitoring of wound healing. Lasers Surg. Med. © 2020 Wiley Periodicals LLC.

Application of OCT-Derived Attenuation Coefficient in Acute Burn-Damaged Skin.

BACKGROUND AND OBJECTIVES: There remains a need to objectively monitor burn wound healing within a clinical setting, and optical coherence tomography (OCT) is proving itself one of the ideal modalities for just such a use. The aim of this study is to utilize the noninvasive and multipurpose capabilities of OCT, along with its cellular-level resolution, to demonstrate the application of optical attenuation coefficient (OAC), as derived from OCT data, to facilitate the automatic digital segmentation of the epidermis from scan images and to work as an objective indicator for burn wound healing assessment. STUDY DESIGN/MATERIALS AND METHODS: A simple, yet efficient, method was used to estimate OAC from OCT images taken over multiple time points following acute burn injury. This method enhanced dermal-epidermal junction (DEJ) contrast, which facilitated the automatic segmentation of the epidermis for subsequent thickness measurements. In addition, we also measured and compared the average OAC of the dermis within said burns for correlative purposes. RESULTS: Compared with unaltered OCT maps, enhanced DEJ contrast was shown in OAC maps, both from single A-lines and completed B-frames. En face epidermal thickness and dermal OAC maps both demonstrated significant changes between imaging sessions following burn injury, such as a loss of epidermal texture and decreased OAC. Quantitative analysis also showed that OAC of acute burned skin decreased below that of healthy skin following injury. CONCLUSIONS: Our study has demonstrated that the OAC estimated from OCT data can be used to enhance imaging contrast to facilitate the automatic segmentation of the epidermal layer, as well as help elucidate our understanding of the pathological changes that occur in human skin when exposed to acute burn injury, which could serve as an objective indicator of skin injury and healing.

Optical coherence tomography for the investigation of skin adaptation in lower limb prosthesis users.

Introduction: Mechanically induced skin breakdown is a significant problem for many lower-limb prosthesis users. It is known that skin can adapt to the mechanical stresses of prosthesis use thereby reducing the risk of breakdown, yet little is understood about the biology behind skin adaptation. This is a proof-of-concept study for the use of novel, noninvasive optical coherence tomography (OCT) imaging techniques to investigate skin adaptation. Methods: Two OCT imaging-based tests were used to evaluate features of the skin that may be involved in adaptation to limb-socket interface stresses. The tests were used to assess the function and structure of the cutaneous microvasculature, respectively. Epidermal thickness was also quantified. Tests were run on three lower-limb prosthesis users in a region of the residual limb believed to be highly stressed within the prosthetic socket. The measurements were compared with measurements taken at a location-matched site on the contralateral limb. Results: Two of three participants demonstrated a faster time-to-peak and larger peakmagnitude reactive hyperemia response in their residual limb compared with their contralateral limb. Two of three participants also demonstrated a larger magnitude vessel density at maximum dilation in their residual limb versus contralateral limb. The epidermal thickness was greater in the residual limb versus contralateral limb for all participants. Conclusions: This study demonstrated the utility of two novel OCT imaging techniques for investigating skin adaptation in users of lower-limb prostheses. If we are able to confirm these findings on a larger subject population, we will better understand the biology behind mechanically induced skin adaptation. These findings, along with the noninvasive OCT imaging methods introduced here, would have the potential to improve clinical practice by enabling the development of rehabilitation techniques and therapeutics to better strengthen skin, thereby reducing the incidence of harmful skin breakdown.

Handheld swept-source optical coherence tomography guided by smartphone-enabled wide-field autofluorescence photography for imaging facial sebaceous glands.

We report a method to image facial sebaceous glands (SGs) using smartphone-enabled wide-field autofluorescence photography (AFP) and handheld swept-source optical coherence tomography (SS-OCT). Smartphone-enabled AFP provides a 2D wide-field fluorescence image that is used both as a functional mapping of the sebum and a positioning guidance for OCT imaging of the SG. Following the guidance, handheld SS-OCT conducts the volume scan to investigate depth-resolved conditions of the SG in the selected regions of interest. We show the results from smartphone-enabled AFP and handheld SS-OCT to demonstrate the ability of our method to image facial SGs, potentially useful for the assessment of skin conditions in dermatology and cosmetology.

Optical coherence tomography for the investigation of skin adaptation to mechanical stress.

BACKGROUND: Skin breakdown due to limb-socket interface stress is a significant problem for lower limb prosthesis users. While it is known that skin can adapt to stress to become more resistant to breakdown, little is understood about skin adaptation and few methods exist to noninvasively investigate it. In this study, we present novel, noninvasive imaging methods using Optical Coherence Tomography (OCT) to assess key features of the cutaneous microvasculature that may be involved in skin adaptation. MATERIALS AND METHODS: Eight able-bodied participants wore a modified below-knee prosthetic socket for two weeks to stress the skin of their lower limb. Two OCT-based imaging tests were used to assess the function and structure, respectively, of the cutaneous microvasculature at multiple time points throughout the socket wear protocol. RESULTS: A measurable reactive hyperemia response was reliably induced in the skin of study participants in the vascular function assessment test. The vascular structure assessment demonstrated excellent field-of-view repeatability, providing rich data sets of vessel structure. No statistically significant differences were found in any of the measurements when compared between time points of the adaptation protocol. The participants' limbs were likely not stressed enough by the able-bodied socket to induce measurable skin adaptation. CONCLUSION: This study introduced new techniques to investigate skin adaptation to mechanical stress. If the key limitations are addressed, these methods have the potential to provide insight into the function and structure of the cutaneous microvasculature that previously could not be attained noninvasively.

Pericyte constriction underlies capillary derecruitment during hyperemia in the setting of arterial stenosis.

Capillary derecruitment distal to a coronary stenosis is implicated as the mechanism of reversible perfusion defect and potential myocardial ischemia during coronary hyperemia; however, the underlying mechanisms are not defined. We tested whether pericyte constriction underlies capillary derecruitment during hyperemia under conditions of stenosis. In vivo two-photon microscopy (2PM) and optical microangiography (OMAG) were used to measure hyperemia-induced changes in capillary diameter and perfusion in wild-type and pericyte-depleted mice with femoral artery stenosis. OMAG demonstrated that hyperemic challenge under stenosis produced capillary derecruitment associated with decreased RBC flux. 2PM demonstrated that hyperemia under control conditions induces 26 ± 5% of capillaries to dilate and 19 ± 3% to constrict. After stenosis, the proportion of capillaries dilating to hyperemia decreased to 14 ± 4% (P = 0.05), whereas proportion of constricting capillaries increased to 32 ± 4% (P = 0.05). Hyperemia-induced changes in capillary diameter occurred preferentially in capillary segments invested with pericytes. In a transgenic mouse model featuring partial pericyte depletion, only 14 ± 3% of capillaries constricted to hyperemic challenge after stenosis, a significant reduction from 33 ± 4% in wild-type littermate controls (P = 0.04). These results provide for the first time direct visualization of hyperemia-induced capillary derecruitment distal to arterial stenosis and demonstrate that pericyte constriction underlies this phenomenon in vivo. These results could have important therapeutic implications in the treatment of exercise-induced ischemia. NEW & NOTEWORTHY In the setting of coronary arterial stenosis, hyperemia produces a reversible perfusion defect resulting from capillary derecruitment that is believed to underlie cardiac ischemia under hyperemic conditions. We use optical microangiography and in vivo two-photon microscopy to visualize capillary derecruitment distal to a femoral arterial stenosis with cellular resolution. We demonstrate that capillary constriction in response to hyperemia in the setting of stenosis is dependent on pericytes, contractile mural cells investing the microcirculation.

Evaluating changes of blood flow in retina, choroid, and outer choroid in rats in response to elevated intraocular pressure by 1300 nm swept-source OCT.

We report the development of a 1300 nm swept-source optical coherence tomography (SS-OCT) system specifically designed to perform OCT imaging and optical microangiography (OMAG) in rat eyes in vivo and its use in evaluating the effects of intraocular pressure (IOP) elevation on ocular circulation. The swept laser is operated in single longitude mode with a 90 nm bandwidth centered at 1300 nm and 200 kHz A-line rate, providing remarkable sensitivity fall-off performance along the imaging depth, a larger field of view of 2.5 × 2.5 mm2 (approximately 35°), and more time-efficient imaging acquisition. The advantage of the SS-OCT/OMAG is highlighted by an increased imaging depth of the entire posterior thickness of optic nerve head (ONH) and its surrounding vascular anatomy, to include, for the first time in vivo, the vasculature at the scleral opening, allowing visualization of the circle of Zinn-Haller and posterior ciliary arteries (PCAs). Furthermore, the capillary-level resolution angiograms achieved at the retinal and choroidal layers over a larger field of view enable a significantly improved quantification of the response of vascular area density (VAD) to elevated IOP. The results indicate that reduction in perfusion of the choroid in response to elevated IOP is delayed compared to that seen in the retina; while choroidal VAD doesn't reach 50% of baseline until ~70 mmHg, the same effect is seen for the retinal VAD at ~60 mmHg. The superior image quality offered by SS-OCT may allow more comprehensive investigation of IOP-related ocular perfusion changes and their pathological roles in glaucomatous optic nerve damage.

Electrically tunable lens integrated with optical coherence tomography angiography for cerebral blood flow imaging in deep cortical layers in mice.

We report the use of an electrically tunable lens (ETL) in a 1.3 µm spectral-domain optical coherence tomography (SD-OCT) system to overcome the depth of focus (DOF) limitation in conventional OCT systems for OCT angiography (OCTA) in a mouse cerebral cortex. The ETL provides fast and dynamic control of the axial focus of the probe beam along the entire range of the mouse cortex, upon which we performed cerebral blood flow imaging of all cortical layers by stitching the OCTA images automatically captured at six focal depths. Capillary vasculature and axial blood flow velocity were revealed in distinctive cortical layers and, for the first time, to the best of our knowledge, in white matter. The results have shown the system capability to conveniently investigate the hemodynamics in deep cortical layers in the mouse brain. More importantly, the compact integration of an ETL will benefit the future design of handheld or intra-cavity OCT probes for a wide range of applications in research and clinical fields.