In vivo Measurement of Intraosseous Vascular Haemodynamic Markers in Human Bone Tissue Utilising Near Infrared Spectroscopy

Abstract

Objective: Poor vascular health is associated with reduced bone strength and increased risk of fragility fracture. However, direct measurement of intraosseous vascular health is difficult due to the density and mineral content of bone. We investigated the feasibility of using a commercially available continuous wave near infrared spectroscopy (NIRS) system for the investigation of vascular haemodynamics in human bone in vivo. Approach: An arterial occlusion (AO) protocol was developed for obtaining haemodynamic measurements of the proximal tibia and lateral calf, including assessment of the protocol's intra operator reproducibility. For 36 participants, intraosseous haemodynamics derived by NIRS were compared to alternative tests of bone health based on dual x-ray absorptiometry (DXA) testing and MRI. Main Results: Near infrared spectroscopy markers of haemodynamics of the proximal tibia demonstrated acceptable reproducibility, comparable with reproducibility assessments of alternative modalities measuring intraosseous haemodynamics, and the use of NIRS for measuring muscle. Novel associations have been demonstrated between haemodynamic markers of bone measured with NIRS and body composition and bone mineral density (BMD) measurements obtained with both DXA and MRI. Significance: Near infrared spectroscopy provides inexpensive, non-invasive, safe, and real time data on changes in oxygenated and deoxygenated haemoglobin concentration in bone at the proximal tibia. This study has demonstrated the potential for NIRS to contribute to research investigating the pathophysiological role of vascular dysfunction within bone tissue, but also the limitations and need for further development of NIRS technology.

Keywords: bone; haemodynamic analysis; near infrared spectroscopy; tibia; vascular physiology.

Figure 1

Arterial occlusion (AO) set up. Occlusion is set at the distal femur with NIRS optodes positioned at the right proximal tibia and lateral calf, secured and shielded with tubular bandages. A temperature optode and O₂C optode is placed at the dorsal surface of the right foot. Inset: Example placement of NIRS optodes on the medial plane of the right proximal tibia. Measurements were taken at the left leg unless prohibited by a previous unilateral medical issue (such as previous fracture, varicose veins, etc.).

Figure 2

Graphical representation of the haemodynamic NIRS markers assessed during occlusion and post occlusion release. Haemodynamic markers are: (1) Baseline TOI at rest prior to the occlusion [TOI_rest; (%)]. (2) Rate of TOI decrease in the last 60s of occlusion [TOI_DO_ 60s (%/s)]. (3) Absolute change in TOI DO [TOI_DO_absΔ (%)]. (4) Rate of TOI increase in first 20s PO release [TOI_PO_20s (%/s)]. (5) Maximal absolute change in TOI post occlusion [TOI_PO_absΔ (%)]. (6) Rate of HHb increase in the last 60s of occlusion [HHb_DO_60s (μM.cm/s)]. (7) Absolute change in HHb during occlusion [HHb_DO_absΔ (μM.cm)]. (8) Rate of O₂Hb decrease in the last 60s of occlusion [O₂Hb_DO_60s (μM.cm/s)]. (9) Absolute change in O₂Hb DO [O₂Hb_DO_absΔ (μM.cm)]. (10) Rate of O₂Hb increase in first 20s post occlusion release [O₂Hb_PO_20s (μM.cm/s)]. (11) Maximal absolute change in O₂Hb post occlusion [O₂Hb_PO_absΔ (μM.cm)]. (12) Observation that the change in nTHI is less than 5% during the 60s period and within 15% change across the 4min occlusion. TOI, total oxygenation index; HHb, deoxygenated haemoglobin; O₂Hb, oxygenated haemoglobin; DO, during occlusion; and PO, post occlusion.

Figure 3

Graphical demonstration of test/retest scores of the TOI_DO_60s marker for the proximal tibia and lateral calf representing the rate of TOI reduction during the last 60s of arterial occlusion. The relatively low between-participant variation at the proximal tibia contributes to a lower ICC score than at the lateral calf [0.28 (95%CI −0.14–0.62) vs. 0.74 (95%CI 0.51–0.87), respectively], despite comparable root mean square coefficient of variation (RMSCV) with the lateral calf [16.3% (95%CI 0–36.3%) vs. 17.2% (95%CI 1.2–33.3%), respectively].

Figure 4

Graphical demonstration of the minimal post occlusive reactive hyperaemic (PORH) response seen at the proximal tibia compared with the lateral calf in one individual participant. Unlike the tibia, the TOI of the calf is seen to “overshoot” the baseline TOI measurement indicated by the purple arrow.

Figure 5

Summary of mean haemodynamic markers for both the proximal tibia and lateral calf stratified by sex [male=dark (n=22); female=light (n=14)], based on the best performing haemodynamic markers from reproducibility assessment. Error bars represent 95% CIs of mean values and ^*denotes statistically significant differences (value of p<0.05) based on independent t-tests between sexes.