Ingemar Fredriksson

The aim of this study was to evaluate microcirculatory perfusion and oxygen saturation in the foot sole of patients with chronic limb-threatening ischemia (CLTI) before and after endovascular intervention using a novel multimodal imaging system. This single-centre observational cohort study included patients with CLTI due to infrainguinal arterial disease, scheduled for endovascular intervention over an 11-month period. Inclusion required a CLTI diagnosis and at least one of: hemodynamic transcutaneous partial pressure of oxygen (TcPO ₂ ) <30 mmHg, toe pressure (TP) <30 mmHg, ankle-brachial index (ABI) <0.4, or ankle pressure <50 mmHg. For patients with diabetes, the TP threshold was adjusted to <50 mmHg. Measurements were performed preoperatively, early postoperatively, and at 1-month follow-up using a multimodal optical system combining multi-exposure laser speckle contrast imaging and multispectral imaging to assess real-time microvascular perfusion and oxygen saturation. Conventional measures (toe pressure, TcPO₂, ABI) were used for comparison. Twenty-five patients were included: 20 successfully revascularized and five serving as a comparison group. Early postoperative results in the revascularized group showed significant increases in TcPO₂ (p=0.004) and – in the combined region of interest – microcirculatory median perfusion (p=0.004), perfusion pulsatility (p<0.001), and oxygen saturation (p=0.01). At 1 month, TcPO₂ (p=0.006), TP (p=0.002) and perfusion pulsatility (p=0.002) remained significantly elevated, whereas median perfusion (p=0.642) and oxygen saturation (p=0.397) returned to baseline levels. No significant changes were observed in the comparison group. The multimodal imaging system detected early microcirculatory improvements after endovascular intervention. While perfusion and oxygen saturation average levels increased early but transiently, sustained increases in perfusion pulsatility suggest it being a marker of improved and lasting microvascular recovery.

BACKGROUND: Overall, 75% of patients with acute stroke have elevated mean arterial pressure (MAP). In randomized stroke trials, the indirect NO donor glyceryl trinitrate lowered MAP but improved neither regional cerebral blood flow (rCBF) nor functional outcomes. One probable reason is that the microcirculation cannot bioactivate glyceryl trinitrate. In contrast, the direct NO donor 3-morpholinosydnonimine (SIN-1), not requiring bioactivation, should also release NO in small vessels, where it supports eNOS (endothelial NO synthase)–derived NO in maintaining rCBF in the hypotensive portion of Lassen autoregulatory curve. In a meta-analysis, SIN-1 reduced infarct volume in ischemia models, but the effects of SIN-1 on early pathophysiology are unknown. METHODS: Here, we investigated SIN-1 during a 60-minute bilateral common carotid artery occlusion and reperfusion in forty-eight 12- to 14-week-old Wistar-Kyoto rat (WKY) controls and 48 stroke-prone spontaneously hypertensive rats. We calculated the difference between the median values of each variable in the last 5 minutes of bilateral common carotid artery occlusion and baseline and compared them between treatment (SIN-1/control) and strain (stroke-prone spontaneously hypertensive rat/WKY) using 2-way ANOVA. We proceeded in the same way regarding reperfusion. RESULTS: Strain×intervention interaction was only found for MAP during bilateral common carotid artery occlusion. SIN-1 lowered MAP within stroke-prone spontaneously hypertensive rats ( P P P =0.038). Across stroke-prone spontaneously hypertensive rat and WKY, SIN-1 increased rCBF ( P P =0.002), lowered extracellular potassium concentration ( P =0.009) and area under the curve of potassium ( P =0.025), and reduced the direct current–amplitude ( P =0.028) and cumulative direct current–shift duration ( P =0.001), consistent with milder ischemia and less severe spreading depolarization load in SIN-1–treated animals. During reperfusion, SIN-1 lowered MAP ( P P =0.002), increased rCBF ( P P P =0.008) and direct current potential ( P =0.022) in both strains, consistent with less no-reflow and better recovery in SIN-1–treated animals. CONCLUSIONS: SIN-1 emerges as a promising antihypertensive in acute stroke as it paradoxically increases rCBF in ischemic tissue and reduces no-reflow.

Knowing the optical properties of tissue is of central importance in accurately modeling light propagation.¹ These optical properties describe photon scattering and absorption in tissue and can be used to simulate the amount of backscattered light from an illuminated tissue surface using diffusion theory or the Monte Carlo technique. In in vivo bio-optical applications, it is common to design instruments that make use of inverse modeling for estimating these properties from spatially, temporarily, and/or spectrally resolved diffusely backscattered light intensities. One such instrument is the PeriFlux 6000 EPOS (enhanced perfusion and oxygen saturation) system in which inverse Monte Carlo is used to analyze spatially and spectrally resolved data to estimate parameters of direct clinical values including hemoglobin tissue fraction and oxygen saturation.^{2 – 4}

We present in vivo optical properties of skin tissue assessed using spatially resolved diffuse reflectance spectroscopy. Data was collected in a sub-study of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Measurements were performed on 3,809 subjects, 50-65 years, on the volar side of the forearm with the PeriFlux 6000 EPOS system. The analysis consisted of an inverse Monte Carlo method where modeled spectra were non-linearly fitted to measured diffuse reflectance spectra at 0.4 and 1.2-mm source-detector fiber separations, respectively, between 475 and 850 nm. The model consisted of one epidermis layer with adaptable thickness and absorption caused by melanin, and two dermis layers. The upper dermis had a fixed thickness of 0.2 mm and the lower an infinite thickness. The absorption in the dermis layers depended on varying amounts of hemoglobin and its oxygen saturation. The reduced scattering coefficient, with three adaptable parameters, was equal in all layers in the model. Absorption coefficient in epidermis times epidermis thickness, reflecting the total amount of melanin, was 0.19±0.16 [-] at 570 nm with a significant difference between winter (0.12±0.10) and summer (0.26±0.19). Melanin absorption implies an average of 3.9% tissue fraction of melanosomes in epidermis. Absorption coefficient at the 570 nm isosbestic point was 0.19±0.11 mm^-1 in the upper dermis layer and 0.10±0.05 mm^-1 in the lower. The reduced scattering coefficient was 2.3±0.5 mm-1 at 570 nm. Average sampling depth for all wavelengths and both separations was 0.43±0.03 mm.