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Regulation of Microvascular Blood Flow: a clinical and experimental study based on laser Doppler perfusion imaging
Linköping University, Department of Medical and Health Sciences, Anesthesiology. Linköping University, Department of Biomedicine and Surgery, Plastic Surgery, Hand Surgery and Burns. Linköping University, Faculty of Health Sciences.
2001 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Local blood flow reflexes in the foot skin of healthy controls and in young diabetic patients with or without nerve dysfunction have been studied using laser Doppler perfusion imaging (LDPI). A neurophysiological follow-up study on nerve dysfunction is presented as a complerhent to the work on blood flow regulation in the young diabetics.

An enhanced high-resolution LDPI (EHR-LDPI), intended for visualization and interpretation of flow dynamics in separate microvessels, has been adapted and evaluated in in vitro tube models and in an in vivo tissue model (hamster cheek pouch). By focusing the laser beam to 40 µm in the focal plane and reducing the step length to 25 µm, full format images (4096 measurement sites) of microvascular tissue areas as small as 1,5 x 1,5 mm were created.

The objectives of the work were to study if the vasoconstrictor response seen during change in posture is a mechanism elicited by a rise in venous pressure, but also to investigate if young diabetic patients with nerve dysfunction have an impairment in the local regulation of foot skin blood flow (postural vasoconstriction and hyperemic response) compared to diabetics without nerve dysfunction. An additional aim was to elucidate whether abnormal nerve conduction is retarded or even prevented by tight metabolic control in patients with type 1 diabetes mellitus.

The experimental studies aimed to improve the resolution of the EHR-LDPI system, to evaluate the system flow response in an in vitro model and to evaluate the performance, the limitations and the future potentials by studying flow dynamics in a tissue containing separate microvessels. It was concluded that:

(1) The LDPI recorded skin perfusion during variations in venous stasis and posture, adding information on flow distribution changes. The difference in flow distribution seen suggested an additive regulatory mechanism to a venoarteriolar reflex during change in posture.

(2) Subclinical nerve conduction defects were more common than microvascular abnormalities as measured by LDPI in the present models in young diabetic patients. Although, no signs of established retinopathy or nephropathy in this patient group, resting skin blood flow abnormalities were present, and these findings were related to high HbA1c-levels.

(3) Tight longwterm metabolic control, with HbA1c values less than 6,5%, could retard nerve dysfunction in patients with type 1 diabetes mellitus and a mean disease duration of 12 years.

(4) Using EHR-LDPI a decrease in signal level was obtained as the tube diameter increased, although the algorithm scaled linearly with velocity and was found not to be sensitive to hematocrit variations. Individual microvessel diameters could be estimated, which on average resulted in a difference of 11 µm compared to microscopic measurements.

(5) A dynamic overview of the vascular tree with volumetric flow estimate as well as RBC velocities of separate vessels was obtained. The need for further focusing of the beam and reduction of the step length appeared to be important tasks to solve in order to get a more accurate vessel diameter determination and to refine the volumetric flow estimate.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2001. , 60 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 683
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-27484Local ID: 12138ISBN: 91-7219-977-6 (print)OAI: oai:DiVA.org:liu-27484DiVA: diva2:248036
Public defence
2001-06-01, Berzeliussalen, Universitetssjukhuset, Linköping, 13:00 (Swedish)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-07Bibliographically approved
List of papers
1. Heterogeneous blood flow response in the foot on dependency, assessed by laser Doppler perfusion imaging
Open this publication in new window or tab >>Heterogeneous blood flow response in the foot on dependency, assessed by laser Doppler perfusion imaging
1997 (English)In: Acta Physiologica Scandinavica, ISSN 0001-6772, E-ISSN 1365-201X, Vol. 159, no 2, 101-106 p.Article in journal (Refereed) Published
Abstract [en]

The exact nature of the decrease in foot skin blood flow seen after a change in posture remains unsettled. This mechanism has previously been examined by non-invasive techniques such as the laser Doppler perfusion monitor (laser Doppler flowmetry). Taking into account the shortcomings of laser Doppler perfusion monitoring when applied to the determination of skin blood flow, which normally shows substantial heterogeneity, we have applied an emerging technology, the laser Doppler perfusion imager (LDPI). This technique provides a more comprehensive picture of the blood flow distribution in the skin, as it maps skin blood flow over a surface area (120×120 mm, 4096 measurement sites). It was used to examine if the reduction in tissue perfusion or the alterations in flow distributions seen after a change in posture (supine to dependency) could be fully explained by an increase in venous pressure (venous stasis of 50 mmHg) or if the data suggest a complementary mechanism.

Skin blood flow of the forefoot decreased from 0.60 V (volt) (median) during rest to 0.40 and 0.38 V during venous stasis and dependency, respectively. Although almost identical median values were obtained during stasis and dependency, the flow distributions were different, with a loss of high flow values during venous stasis. Biological zero was 0.24 V.

As the LDPI technique readily records skin perfusion during variations in venous stasis and posture, as well as information on flow distribution changes, it appears promising for future application in stimuli-response studies of skin blood flow. The difference in flow distribution seen between increased venous pressure and dependency suggests an additive regulatory mechanism to the veni-vasomotor reflex during a change in posture.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81118 (URN)10.1046/j.1365-201X.1997.587345000.x (DOI)
Available from: 2012-09-07 Created: 2012-09-07 Last updated: 2017-12-07Bibliographically approved
2. Testing microvascular function in children and adolescents with diabetes using laser Doppler perfusion imaging: implications on flow models and measurement sites
Open this publication in new window or tab >>Testing microvascular function in children and adolescents with diabetes using laser Doppler perfusion imaging: implications on flow models and measurement sites
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

The purpose of the present study was to examine if functional impairment of the skin microvasculature is present in young diabetic patients with and without neurophysiological signs of nerve dysfunction. Dorsal foot skin blood flow was measured in young diabetics and controls using laser Doppler perfusion irnaging (LDPI). Blood flow was- measured during supine resting flow, during change in posture and during post occlusive hyperemia. Peripheral nerve function was measured by electrophysiological studies of peroneal and sural nerve conduction. Fifty seven (57%) percent of the diabetic patients had abnormal nerve conduction in two or several nerves. Diabetics with poor metabolic control (HbAlc > 7,5 %) showed an increase in supine resting blood flow compared to better regulated diabetics and controls. No other differences in skin blood flow between diabetics and controls were seen. During change in posture, blood flow increased instead of decreased in a majority of the study subjects. Low resting blood !low levels are suggested to contribute to this absence of postural vasoconstrictor response. It is concluded that nerve conduction defects arc much more common than microvascular abnormalities measured by LDPI in the present models in young diabetic patients. Our recommendation is to increase basal resting flow before applying vasoconstricting models in yotmg subjects when using LDPI in low flow areas, as the foot skin.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81119 (URN)
Available from: 2012-09-07 Created: 2012-09-07 Last updated: 2012-09-07
3. Nerve conduction defects are retarded by tight metabolic control in type I diabetes
Open this publication in new window or tab >>Nerve conduction defects are retarded by tight metabolic control in type I diabetes
2001 (English)In: Muscle and Nerve, ISSN 0148-639X, E-ISSN 1097-4598, Vol. 24, no 2, 240-246 p.Article in journal (Refereed) Published
Abstract [en]

This follow-up study examines whether the development of nerve dysfunction is retarded by tight metabolic control in patients with type I diabetes mellitus. Seventy-one patients and 115 age-matched healthy control subjects underwent studies of nerve conduction in peroneal and sural nerves. The presence of diabetes was associated with a reduction in peroneal motor nerve conduction velocity (MCV) by 5.9 m/s, sural sensory nerve conduction velocity (SCV) by 3.4 m/s, and sural sensory nerve action potential (SNAP) amplitude by 22%. Dysfunction in peroneal MCV, sural SCV, and sural SNAP were related to long-term poor metabolic control. Eleven of 12 patients with HbA1c <6.5% had normal nerve conduction or abnormality in only one nerve as compared to 2 of 15 patients with HbA1c >8.0%. It is concluded that tight long-term metabolic control (HbA1c <6.5%) can retard nerve dysfunction in patients with type I diabetes mellitus and a mean disease duration of 12 years.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-25930 (URN)10.1002/1097-4598(200102)24:2<240::AID-MUS90>3.0.CO;2-2 (DOI)10374 (Local ID)10374 (Archive number)10374 (OAI)
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-09-07Bibliographically approved
4. Evaluation of Enhanced High-Resolution Laser Doppler Imaging in an in Vitro Tube Model with the Aim of Assessing Blood Flow in Separate Microvessels
Open this publication in new window or tab >>Evaluation of Enhanced High-Resolution Laser Doppler Imaging in an in Vitro Tube Model with the Aim of Assessing Blood Flow in Separate Microvessels
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1998 (English)In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 56, no 3, 261-270 p.Article in journal (Refereed) Published
Abstract [en]

An enhanced high-resolution laser Doppler imaging (EHR-LDI) technique intended for visualization of separate microvessels was evaluated by use ofin vitroflow models. In EHR-LDI, a laser beam focused to a half-power diameter less than 40 μm successively scans the tissue under study in steps of 25 μm. Spatial blood flow variations within microvascular structures of 1.5 × 1.5 mm are rendered by 64 × 64 measurement sites. Individual microvessel diameters could be estimated and an average difference of 11 μm compared to microscopic measurements was obtained. For the flow algorithm used, the LDI output signal was found to scale linearly with average velocity (0–3.5 mm/s) when a plastic tube of inner diameter 175 μm was perfused with human blood (correlation coefficient 0.99). The LDI output signal was further found insensitive to hematocrit variations in the range 16–44%. Due to the limited laser light penetration in blood, a reduction in the LDI output signal was observed as the inner tube diameters were successively changed from 280 to 1400 μm.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-32562 (URN)10.1006/mvre.1998.2095 (DOI)18475 (Local ID)18475 (Archive number)18475 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-09-07Bibliographically approved
5. Red Blood Cell Velocity and Volumetric Flow Assessment by Enhanced High-Resolution Laser Doppler Imaging in Separate Vessels of the Hamster Cheek Pouch Microcirculation
Open this publication in new window or tab >>Red Blood Cell Velocity and Volumetric Flow Assessment by Enhanced High-Resolution Laser Doppler Imaging in Separate Vessels of the Hamster Cheek Pouch Microcirculation
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1999 (English)In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 58, no 1, 62-73 p.Article in journal (Refereed) Published
Abstract [en]

An enhanced high-resolution laser Doppler imager (EHR-LDI), configured to fit the demands of a measurement area containing separate microvessels, was evaluated for perfusion measurements in hamster cheek pouch preparations during ischemia, reperfusion, and pharmacologically induced vasodilation and vasoconstriction. Measurements in separate microvessels where the laser beam was smaller than the vessel diameter were referred to as red blood cell (RBC) velocity estimates, as previously validated in vitro, whereas a relative flow index, RFI (mean RBC velocity/tissue area), was introduced as a volumetric flow measure. Microvessel diameter and RBC velocity changes during ischemia, reperfusion, as well as during vasoconstriction and vasodilation correlated to the data obtained from the microscope. Correspondingly, during the described provocations anticipated volumetric flow changes were registered as changes in the RFI. When data on intravessel RBC velocity profiles are presented they reflect a parabolic flow profile usually seen in this size microvessel. The EHR-LDI appears a promising tool for investigation of the microvasculature, as it almost simultaneously provides information on relative changes of both in vivo RBC velocity and volumetric flow (RFI), although the latter estimate needs to be further refined.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-32567 (URN)10.1006/mvre.1999.2150 (DOI)18481 (Local ID)18481 (Archive number)18481 (OAI)
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-09-07Bibliographically approved

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