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Photon migration in tissue: laser induced fluorescence for cancer diagnostics and influence of optical properties on microvascular Doppler spectroscopy
Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Laser induced flourescence (LIF) is an "optical biopsy" method, based on the selective accumulation of fluorophores in neoplastic tissue. Two recently developed, non-photosensitizing tumor seeking carotenoporphyrins were assessed regarding tumor selectivity, and biodistribution, in experimental animals. A tumor to peritumoral ratio of 5-6:1 was seen in the background free substance related fluorescence in vivo, as well as ex vivo. Cerebral cortex and skeletal muscle displayed a low, and liver a high substance related fluorescence.

Laser Doppler flowmetry (LDF) is based on the spectral broadening of monochromatic light, that interacts with moving red blood cells in tissue. The power spectral density of the backscattered light can be processed to yield an estimate of microvascular tissue perlusion. Using a Monte Carlo simulation model of human skin, it is demonstt·ated that for a particular light delivery/detection arrangement, Doppler shifted photons that originate from the central core and peripheral parts of blood vessels of physiological dimensions, both contribute to the detected signal. Further, more than 10 times as many photons will interact with the superficial as with the deep vascular plexus. However, due to greater velocities and concentrations of the moving scatterers, the profound circulation still may yield a greater contribution to the LDF perfusion estimate.

A multiple polynomial regression method for prediction of photon pathlength and optical properties in tissue, at surlace source detector separations up to two millimeters, was developed. Using the diffuse, backscattered reflectance profile from an array of optical sensors as predictors in the model resulted in root-meansquare errors of less than three per cent for the estimated pathlength. Caucasian human skin displayed a maximum in vivo variation of ~35 % in the photon pathlength between individuals in similar locations, and within individuals comparing fingertip and forearm skin, as a result of varying optical properties.

Assuming a homogenous tissue perlusion, the pathlength variations will induce a corresponding variation in the LDF petfusion signal, which can be compensated for by linearization and pathlength normalization, making intra- and interindividual comparisons of the LDF perfusion estimate feasible.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet , 2002. , 123 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 735
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-29435Local ID: 14781ISBN: 91-7373-179-X (print)OAI: oai:DiVA.org:liu-29435DiVA: diva2:250250
Public defence
2002-05-31, Administrationsbyggnadens aula, Universitetssjukhuset, Linköping, 13:15 (Swedish)
Opponent
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-10-08Bibliographically approved
List of papers
1. Laser-induced fluorescence in malignant and normal tissue in mice injected with two different carotenoporphyrins
Open this publication in new window or tab >>Laser-induced fluorescence in malignant and normal tissue in mice injected with two different carotenoporphyrins
Show others...
1994 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 70, no 5, 873-879 p.Article in journal (Refereed) Published
Abstract [en]

Laser-induced fluorescence (LIF) was used to characterise the localisation of an intravenously administered trimethylated carotenoporphyrin [CP(Me)3] and a trimethoxylated carotenoporphyrin [CP(OMe)3] in an intramuscularly transplanted malignant tumour (MS-2 fibrosarcoma) and healthy muscle in female Balb/c mice, 3, 24, 48 and 96 h post injection. The fluorescence was induced with a dye laser pumped by a nitrogen laser, emitting light at 425 nm. The fluorescence spectra were recorded in the region 455-760 nm using a polychromator equipped with an image-intensified CCD camera. The tumour/peritumoral muscle ratio was about 5:1 for CP(Me)3 and about 6:1 for CP(OMe)3 in terms of the background-free fluorescence intensity, which peaked at about 655 nm. By including the endogenous tissue fluorescence, the contrast was further enhanced by a factor of approximately 2.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81355 (URN)10.1038/bjc.1994.413 (DOI)
Available from: 2012-09-12 Created: 2012-09-12 Last updated: 2017-12-07Bibliographically approved
2. Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice
Open this publication in new window or tab >>Laser-induced fluorescence studies of the biodistribution of carotenoporphyrins in mice
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1997 (English)In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 76, no 3, 355-364 p.Article in journal (Refereed) Published
Abstract [en]

The biodistribution of two recently developed tumour markers, trimethylated (CP(Me)3) and trimethoxylated (CP(OMe)3) carotenoporphyrin, was investigated by means of laser-induced fluorescence (LIF) after i.v. injection into 38 tumour-bearing (MS-2 fibrosarcoma) female Balb/c mice. At 3, 24, 48 or 96 h after administration, the carotenoporphyrin fluorescence was measured in tumoral and peritumoral tissue, as well as in the abdominal, thoracic and cranial cavities. The fluorescence was induced by a nitrogen laser-pumped dye laser, emitting light at 425 nm, and analysed by a polychromator equipped with an image-intensified CCD camera. The fluorescence was evaluated at 490, 655 and 720 nm: the second and third wavelengths represent the carotenoporphyrin (CP)-related peaks, whereas the first one is close to the peak of the tissue autofluorescence. The tumour and the liver were the two tissue types showing the strongest carotenoporphyrin-related fluorescence, whereas the cerebral cortex and muscle consistently exhibited weak substance-related fluorescence. In most tissue types, the fluorescence intensities decreased over time. A few exceptions were observed, notably the liver, in which the intensity remained remarkably constant over the time period investigated.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81356 (URN)10.1038/bjc.1997.390 (DOI)
Available from: 2012-09-12 Created: 2012-09-12 Last updated: 2017-12-07Bibliographically approved
3. Monte Carlo simulations of the light interaction with blood vessels in human skin in the red wavelength region
Open this publication in new window or tab >>Monte Carlo simulations of the light interaction with blood vessels in human skin in the red wavelength region
1998 (English)In: Proceedings of SPIE, 3252(06),44-53 / [ed] A V Priezzhev, T Asakura, J D Briers, San José: SPIE , 1998, 44-53 p.Conference paper, Published paper (Refereed)
Abstract [en]

An attempt was made at determining if the elastically backscattered Doppler shifted light from cutaneous blood vessels merely emanates from the peripheral parts, or also from the more central core of these vessels, after illumination by red laser light (632 nm). A multilayered, semi-infinite Monte Carlo model of human skin was constructed accordingly, with separate layers or epidermis, dermis including blood, inferior vascular plexus and subcutaneous fat. Two concentric cylinders of infinite length and with varying diameters, representing core and peripheral parts of a blood vessel, were located at various depths in the skin model, either in the superior or inferior vascular plexus. In order to test the stability of the model predictions, widely varying values of the optical properties were employed in the calculations, trying to encompass most of the extreme values found in the literature. The number of photons Doppler shifted by a fixed size central core of a small blood vessel, is independent of the volume of blood surrounding this core in the rest of the blood vessel, provided the total number of detected photons is maintained constant, and the vessel dimensions are within human physiological limits. For the source/detector system simulated (one optical fiber 700 micrometer diameter), backscattered light Doppler shifted in superficial blood vessels constituted almost all the photons detected, with only very few photons having interacted with the inferior plexus.

Place, publisher, year, edition, pages
San José: SPIE, 1998
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-32585 (URN)10.1117/12.311897 (DOI)18499 (Local ID)9780819426918 (ISBN)18499 (Archive number)18499 (OAI)
Conference
Optical Diagnostics of Biological Fluids Ill, Bi0S'98, San Jose, CA, USA, 1998
Available from: 2009-10-09 Created: 2009-10-09 Last updated: 2012-09-12Bibliographically approved
4. Photon pathlength determination based on spatially resolved diffuse reflectance
Open this publication in new window or tab >>Photon pathlength determination based on spatially resolved diffuse reflectance
2002 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, Vol. 7, no 3, 478-485 p.Article in journal (Refereed) Published
Abstract [en]

A method for the prediction of the average photon pathlength in turbid media has been developed. The method is based on spatially resolved diffuse reflectance with discrete source detector distances up to 2 mm. Light reflectance was simulated using a Monte Carlo technique with a one-layer model utilizing a wide range of optical properties, relevant to human skin. At a source detector separation of 2 mm, the pathlength can vary sixfold due to differences in optical properties. By applying various preprocessing and prediction techniques, the pathlength can be predicted with a root-mean-square error of approximately 5%. Estimation of the photon pathlength can be used, e.g., to remove the influence of optical properties on laser Doppler flowmetry perfusion readings, which are almost linearly related to the average photon pathlength.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-24559 (URN)10.1117/1.1482378 (DOI)6721 (Local ID)6721 (Archive number)6721 (OAI)
Available from: 2009-10-07 Created: 2009-10-07 Last updated: 2016-08-31Bibliographically approved
5. In vivo determination of local skin optical properties and perfusion using a pathlength compensated spatially resolved laser Doppler flowmetry approach
Open this publication in new window or tab >>In vivo determination of local skin optical properties and perfusion using a pathlength compensated spatially resolved laser Doppler flowmetry approach
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The laser Doppler flowmetry (LDF) perfusion estimate is almost linearly related to the pathlength of the detected photons, and, consequently, sensitive to the optical properties of the tissue. Therefore, we propose an in vivo pathlength and optical property estimation method, based on diffuse reflectance and Monte Carlo simulations, that minimizes the influence of optical properties on the LDF perfusion estimate. Caucasian human skin displayed a maximrun variation of -35% in the photon pathlength between individuals in similar locations, and within individuals comparing fingertip and forearm skin. The results suggest that, using the proposed method, it is possible to minimize the influence of optical properties, thus enabling intraw and inter-individual compatisons ofLDF perfusion estimates in different organs.

National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-81359 (URN)
Available from: 2012-09-12 Created: 2012-09-12 Last updated: 2016-08-31Bibliographically approved

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