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THE SCIENTIFIC BASIS OF BONE BLOOD FLOW MEASUREMENT



Abstract

Measurement of blood flow to the skeleton is technically challenging. The specific problems of measuring blood flow that are particular to bone are:

  1. i) there are 206 separate bones in the skeleton;

  2. ii) each bone has multiple arterial inputs and venous outflows;

  3. iii) each bone is heterogeneous, comprising varying proportions of cortical bone, cancellous bone, and marrow (both haematopoietic and fatty).

Because of this heterogeneity of the tissue, it is also important to specify precisely the region of bone that is being measured, and this problem accounts for some of the discrepancies in values of bone blood flow quoted in the literature. From a practical orthopaedic perspective, techniques to measure regional blood flow are normally more informative than measurements of total skeletal blood flow.

In experimental studies, the microsphere technique has been used most widely for the quantitative measurement of bone blood flow, and is regarded as the gold standard. Particles of the order of 15 microns in diameter are injected into the ventricle and trapped in the microcirculation during a single passage. The distribution of microspheres in the body is proportional to the distribution of cardiac output, and if a reference arterial blood sample is taken during injection of the microspheres, then blood flow may be calculated. Microspheres are normally labeled with a radioactive tracer or a colored dye, and microsphere number is estimated from assays of the attached label.

The microsphere technique is a specific example of indicator fractionation, and clinically indicator fractionation can be applied using imaging techniques such as magnetic resonance imaging (MRI) or positron emission tomography (PET). MRI-based techniques are based on gadolinium contrast agents, and PET uses positron-emitting isotopes such as oxygen-15 labelled water, fluorine-18 ion, or 18F-fluorodeoxyglucose. Positron-emitting isotopes are short-lived, and need to be produced daily by a cyclotron, limiting the general utility of the technique. However, dynamic PET measurements with fluorine-18 have been used to assess simultaneously both bone blood flow and bone formation rates.

Blood flow can also be estimated from velocity measurements, e.g. electromagnetic flowmetry, laser Doppler, and ultrasound Doppler. Laser Doppler measurements require contact between the probe and the tissue being measured, and have applications in experimental studies of vascular reactivity in bone. Although ultrasound is reflected very effectively from bone surfaces, ultrasound Doppler has been used to image the lumber arteries in patients with degenerative disc disease.

Bone, like other tissues in the body, is relatively transparent to light in the near-infra red, but there are specific absorption peaks for deoxy- and oxy-hemoglobin. This is the basis of near infra-red spectroscopy for perfusion measurements. However, because of the complexities of light scattering in tissue, spatial resolution is poor. Measurements in the proximal tibia are quite straightforward, and we are currently using this technique in studies of bone loss in spinal cord injury patients.

The abstracts were prepared by Lynne C. Jones, PhD. and Michael A. Mont, MD. Correspondence should be addressed to Lynne C. Jones, PhD., at Suite 201 Good Samaritan Hospital POB, Loch Raven Blvd., Baltimore, MD 21239 USA. Email: ljones3@jhmi.edu