Optical and acoustic properties at 1064 nm of polyvinyl chloride-plastisol for use as a tissue phantom in biomedical optoacoustics

A novel optoacoustic phantom made of polyvinyl chloride-plastisol (PVCP) for optoacoustic studies is described. The optical and acoustic properties of PVCP were measured. Titanium dioxide (TiO2) powder and black plastic colour (BPC) were used to introduce scattering and absorption, respectively, in the phantoms. The optical absorption coefficient (mua) at 1064 nm was determined using an optoacoustic method, while diffuse reflectance measurements were used to obtain the optical reduced scattering coefficient (mu's). These optical properties were calculated to be mua = (12.818 +/- 0.001)ABPC cm(-1) and mu's = (2.6 +/- 0.2)S(TiO2) + (1.4 +/- 0.1) cm(-1), where ABPC is the BPC per cent volume concentration, and S(TiO2) is the TiO2 volume concentration (mg mL(-1)). The speed of sound in PVCP was measured to be (1.40 +/- 0.02) x 10(3) m s(-1) using the pulse echo transmit receive method, with an acoustic attenuation of (0.56 +/- 1.01) f(1.51+/-0.06)MHz (dB cm(-1)) in the frequency range of 0.61-1.25 MHz, and a density, calculated by measuring the displacement of water, of 1.00 +/- 0.04 g cm(-3). The speed of sound and density of PVCP are similar to tissue, and together with the user-adjustable optical properties, make this material well suited for developing tissue-equivalent phantoms for biomedical optoacoustics.     

Experimental verification of conditions for near infrared spectroscopy (NIRS).

OBJECTIVES: in vitro assessment of the reproducibility and the optimal separation and position of the optodes in continuous wave (CW-) NIRS measurement of local inhomogeneities in absorption and/or scattering. METHODS: a CW- NIRS system (OXYMON) was used with laser diodes at wavelengths of 767 nm, 845 nm, 905 nm, 945 nm and 975 nm. For practical considerations (dimensions of neonatal head) the measurements were performed on a cylindrical tissue-equivalent phantom (70 mm diameter of base material with mua = 0.01 mm(-1) (800 nm) and mu's = 1.00 mm(-1) (800 nm)), containing rods with 10 x absorption, or 10 x scattering, and 5 x both Monte Carlo simulations were carried out of a cylinder with transport scattering coefficient mu's = 0.525 mm(-1) and absorption coefficient mua = 0.075 mm(-1) and two optode positions. RESULTS: reproducibility of repeated measurements (n = 10) was +/- 0.005 OD. Maximum OD in case of absorbing rod, and of absorbing + scattering rod was measured with optodes separated by 90 degrees and rod position angle symmetrically (45 degrees ) in between. Minimum OD for these rods was obtained with optodes at 150 degrees angle and rod position at 240 degrees (i.e. relative to transmitting optode position at 0 degrees ). A second maximum OD was obtained at an optode angle 180 degrees and rod position at 180 degrees. Maximum OD (i.e. attenuation) for the scattering rod was at optode separation angle of 90 degrees and rod at 0 degrees. Minimum OD for this case was obtained with optode angle of 180 degrees and rod positions around 80 degrees and 280 degrees. Maximum OD changes by absorbing rod were in the order of +0.12 OD and -0.04 OD, respectively. Simulations at an optode separation angle of 90 degrees showed a spatial sensitivity path enclosing the rod position at maximum absorption found experimentally. CONCLUSIONS: when considering the phantom as a realistic geometrical model for the neonatal head, it can be concluded that the optode position at 90 degrees angle would be optimal for detecting an inhomogeneity at 15 mm depth, i.e. the location of the periventricular white matter. Since the rods are relatively strongly different from the base material the question remains to be answered whether local ischemia, which might lead to irreversible brain damage, can be detected by CW-NIRS     

Optical properties of adenocarcinoma and squamous cell carcinoma of the gastroesophageal junction

Photodynamic therapy (PDT) is an alternative to radical surgical resection for T1a or nonresectable carcinomas of the gastroesophageal junction. Besides the concentration of the photosensitizer, the light distribution in tissue is responsible for tumor destruction. For this reason, knowledge about the behavior of light in healthy and dysplastic tissue is of great interest for careful irradiation scheduling. The aim of this study is to determine the optical parameters (OP) of healthy and carcinomatous tissue of the gastroesophageal junction in vitro to provide reproducible parameters for optimal dosimetry when applying PDT. A total of 36 tissue samples [adenocarcinoma tissue (n=21), squamous cell tissue (n=15)] are obtained from patients with carcinomas of the gastroesophageal junction. The optical parameters are measured in 10-nm steps using new integrating sphere spectrometers in the PDT-relevant wavelength range of 300 to 1140 nm and evaluated by inverse Monte-Carlo simulation. Additional examinations are done in healthy tissue from the surgical safety margin. In the wavelength range of frequently applied photosensitizers at 330, 630, and 650 nm, the absorption coefficient in tumor tissue (adenocarcinoma 1.22, 0.16, and 0.15 mm(-1); squamous cell carcinoma 1.48, 0.13, and 0.11 mm(-1)) is significantly lower than in healthy tissue (stomach 3.34, 0.26, and 0.20 mm(-1); esophagus 2.47, 0.21, and 0.18 mm(-1)). The scattering coefficient of all tissues decreases continuously with increasing wavelength (adenocarcinoma 22.8, 12.99, and 12.52 mm(-1); squamous cell carcinoma 19.44, 9.35, and 8.98 mm(-1); stomach 20.55, 13.96, and 13.94 mm(-1); esophagus 20.34, 12.56, and 12.22 mm(-1). All tissues show an anisotropy factor between 0.80 and 0.94 over the entire spectrum. The maximum optical penetration depth for all tissues is achieved in the range of 800 to 1100 nm. At the wavelength range of 330, 630, and 650 nm, the optical penetration depth is significantly higher in carcinoma tissue (adenocarcinoma 0.27, 1.54, and 1.66 mm; squamous cell carcinoma 0.23, 1.71, and 1.84 mm) than in healthy tissue (stomach 0.16, 1.10, and 1.26 mm; esophagus 0.17, 1.47, and 1.65 mm; p<0.05). Above 1000 nm, a higher absorption coefficient of tumor tissue results in a lower optical penetration depth than in healthy tissue (p<0.05). The higher absorption and scattering of the tumor tissue in the wavelength range of available photosensitizer is associated with a low optical penetration depth. This necessitates higher energy doses and long application times or repeated applications to effectively treat large tumor volumes. Photosensitizers optimized for larger wavelength range need to be developed to increase the efficacy of PDT.     

An immunohistochemical analysis of fibroid vasculature

This study aimed to compare vascular parameters between fibroid and myometrium. From 10 uteri, specimens were taken from small fibroids (<0.5 cm), from the inner and outer parts of large fibroids (>3 cm), and from myometrium. Antibodies to endothelial cell markers CD31, CD34, factor VIII-related antigen (FVIII), and Ulex europaeus lectin were used in routine immuno- and lectin chemistry protocols. Parameters calculated were vascular area (VA), microvascular density (MD) and vascular luminal diameter. VA measures showed that myometrium had a greater area stained than small fibroids (P = 0.03) using CD31 and both inner (P = 0.04) and outer (P = 0.01) regions of large fibroids using FVIII, and than all groups (small, P = 0.02; inner, P = 0.02; outer, P = 0.006) using the lectin U. europaeus. MD was higher in myometrium than all uterine fibroid groups (small, P = 0.009; inner, P = 0.01; outer, P = 0.01) using U. europaeus lectin, than both regions of large (inner, P = 0.04; outer, P = 0.02) fibroids using FVIII, and than outer regions of large fibroids using CD31 (P < 0.05). There were significantly larger diameter vessels in myometrium and large fibroids compared with small fibroids using CD34, FVIII and the lectin U. europaeus (P 相似文献   

Fibroids display an anti-angiogenic gene expression profile when compared with adjacent myometrium

The aetiology of uterine fibroids remains unknown, despite causing significant gynaecological morbidity. Fibroids have a reduced microvascular density when compared with adjacent myometrial tissue. The aim of this study was to identify genes with differential expression between fibroid and adjacent normal myometrium, particularly genes with a role in angiogenesis. Total RNA was extracted from fibroid/myometrium pairs from 12 hysterectomy specimens, and used to perform 24 cDNA microarrays. There were 10,500 genes screened on each microarray for differential expression. Analysis of expression data was carried out using multiple t-tests, as well as a novel class prediction algorithm (GeneRaVE). The differential gene expression of selected genes was confirmed by quantitative 'real time' RT-PCR. Selected genes with a role in angiogenesis were further analysed for expression in isolated cell populations of endothelial cells (fibroid and myometrium) and smooth muscle cells (fibroid and myometrium), to see if their expression was confined to particular cell types. Twenty-five genes with differential gene expression between fibroid and myometrium were identified. Insulin-like growth factor-2, endothelin A receptor, connective tissue growth factor (CTGF), cysteine-rich angiogenic inducer 61 (CYR61) and collagen 4alpha2 (COL4A2) were confirmed by RT-PCR. CTGF and CYR61, both angiogenesis promoters, were reduced in expression relative to myometrium. COL4A2, the precursor for an angiogenesis inhibitor, canstatin, was increased relative to myometrium. These three genes display an anti-angiogenic expression profile in fibroids relative to myometrium. These findings may explain the reduced microvascular density seen in fibroids relative to myometrium.     

Optical properties of human skin in the near infrared wavelength range of 1000 to 2200 nm

In this paper we present the absorption coefficient mu(a) and the isotropic scattering coefficient mu(s)(') for 22 human skin samples measured using a double integrating sphere apparatus in the wavelength range of 1000-2200 nm. These in vitro results show that values for mua) follow 70% of the absorption coefficient of water and values for mu(s)(') range from 3 to 16 cm(-1). From the measured optical properties, it was found that a 2% Intralipid solution provides a suitable skin tissue phantom.     

Hysteroscopic myomectomy: a comprehensive review of surgical techniques

Hysteroscopic myomectomy currently represents the standard minimally invasive surgical procedure for treating submucous fibroids, with abnormal uterine bleeding and reproductive issues being the most common indications. While hysteroscopic myomectomy has been shown to be safe and effective in the control of menstrual disorders, its effects on infertility remain unclear. The review provides a comprehensive survey of all hysteroscopic techniques used to treat fibroids found completely within the uterine cavity (G0) and those with intramural development (G1 and G2). MEDLINE and EMBASE searches identified published papers from 1970. The choice of the technique mostly depends on the intramural extension of the fibroid, as well as on personal experience and available equipment. 'Resectoscopic slicing' still represents the 'gold standard' technique for treating fibroids G0, even if several other effective techniques including ablation by neodymium-yttrium-aluminum-garnet laser, morcellation and office myomectomy have been proposed. On the other hand, the present review clearly indicates that there is still no single technique proven to be unequivocally superior for treating fibroids G1 and G2. Most techniques aim at the transformation of an intramural fibroid into a totally intracavitary lesion, thus avoiding a deep cut into the myometrium. At present, the 'cold loop' technique seems to represent the best option as it allows a safe and complete removal of such fibroids in just one surgical procedure, while respecting the surrounding healthy myometrium.     

Assessment of optical path length in tissue using neodymium and water absorptions for application to near-infrared spectroscopy

Quantitative analysis of blood oxygen saturation using near-IR spectroscopy is made difficult by uncertainties in both the absolute value and the wavelength dependence of the optical path length. We introduce a novel means of assessing the wavelength dependence of path length, exploiting the relative intensities of several absorptions exhibited by an exogenous contrast agent (neodymium). Combined with a previously described method that exploits endogenous water absorptions, the described technique estimates the absolute path length at several wavelengths throughout the visible/near-IR range of interest. Isolated rat hearts (n = 11) are perfused separately with Krebs-Henseleit buffer (KHB) and a KHB solution to which neodymium had been added, and visible/near-IR spectra are acquired using an optical probe made up of emission and collection fibers in concentric rings of diameters 1 and 3 mm, respectively. Relative optical path lengths at 520, 580, 679, 740, 800, 870, and 975 nm are 0.41+/-0.13, 0.49+/-0.21, 0.90+/-0.09, 0.94+/-0.01, 1.00, 0.84+/-0.01, and 0.78+/-0.08, respectively. The absolute path length at 975 nm is estimated to be 3.8+/-0.6 mm, based on the intensity of the water absorptions and the known tissue water concentration. These results are strictly valid only for the experimental geometry applied here.     

Tissue differences but limited sex steroid responsiveness of c-fos and c-jun in human fibroids and myometrium

Sex steroids influence the growth of mammalian uterine tissues and the proto-oncogenes c-fos and c-jun have been implicated in the cascade of cellular events induced by the cyclic influence of oestrogen and progesterone. To investigate the role of these proto-oncogenes for fibroid growth their mRNA expression was measured in myometrium and fibroids under different hormonal conditions, using a solution hybridization method. Fibroids and myometrium were collected at surgery from premenopausal, postmenopausal and pregnant women as well as women treated with a gonadotrophin releasing hormone agonist (GnRHa; Goserelin). The phase of the menstrual cycle was determined in all the untreated, premenopausal, non-pregnant women. The mRNA expression of c-fos and c-jun in fibroids was significantly lower than in homologous myometrium. No significant differences in c-fos expression were observed in myometrium, or fibroids, due to menstrual cycle phase, GnRHa treatment, pregnancy or the menopause. The c-jun expression in myometrium from pregnant women without fibroid disease was significantly higher than the corresponding control myometrium from premenopausal, non-pregnant women. These results demonstrate a tissue difference in the expression of c-fos and c-jun between myometrium and fibroids.     

Influence of shear rate on the optical properties of human blood in the spectral range 250 to 1100 nm

The intrinsic optical parameters-absorption coefficient mua, scattering coefficient mus, anisotropy factor g, and effective scattering coefficient mus'--are determined for human red blood cells of hematocrit 42.1% dependent on the shear rate in the wavelength range 250 to 1100 nm. Integrating sphere measurements of light transmittance and reflectance in combination with inverse Monte-Carlo simulation are carried out for different wall shear rates between 0 and 1000 s(-1). Randomly oriented cells show maximal mua, mus, and mus' values. Cell alignment and elongation, as well as the Fahraeus effect at increasing shear rates, lead to an asymptotical decrease of these values. The anisotropy factor shows this behavior only below 600 nm, dependent on absorption; above 600 nm, g is almost independent of shear rate. The decrease of mus' is inversely correlated with the hemoglobin absorption. Compared to randomly oriented cells, aggregation reduces all parameters by a different degree, depending on the hemoglobin absorption. It is possible to evaluate the influence of collective scattering phenomena, the absorption within the cell, and the cell shape.     

Retinoic acid pathway genes show significantly altered expression in uterine fibroids when compared with normal myometrium

Fibroids are benign neoplasms of myometrial smooth muscle cells (SMC). Despite being the most common tumor in humans, their etiology is poorly understood. Recent microarray studies have demonstrated that multiple members of the retinoid pathway are differentially expressed between myometrium and fibroids. The aim of this present study was to investigate gene expression of members of the retinoid pathway in matched myometrium and fibroids. We have demonstrated differential gene expression of two binding proteins [cellular retinol-binding proteins (CRBP) 1 and 2], three enzymes [alcohol dehydrogenase 1 (ADH1), aldehyde dehydrogenase (ALDH1) and retinol dehydrogenase (RODH)] and two receptors [retinoid X receptors (RXR) alpha and gamma] involved in the retinoid pathway by real-time PCR. There were no differences in gene expression for retinoid receptors RARalpha, beta, gamma and RXRbeta, and for the metabolizing enzyme cytochrome P450, family 26 subfamily A. We confirmed results for ADH1, ALDH1, CRBP1 and CRABP2 at the protein level by western blot. Using immunohistochemistry these proteins were mostly localized to myometrial and fibroid SMC. An exception to this was ALDH1 protein, which displayed strong staining localized to cells of the connective tissue, presumably fibroblasts, with a striking differential expression pattern between myometrium and fibroids. These results demonstrate that the retinoid pathway is altered in fibroids when compared with normal myometrium and specifically identify ALDH1 in fibroid fibroblasts. These alterations can lead to aberrant retinoic acid (RA) production and signaling, and alter the expression of RA target genes, which may be an important step in fibroid development.     

Determination of the tumor tissue optical properties during and after photodynamic therapy using inverse Monte Carlo method and double integrating sphere between 350 and 1000 nm

Photodynamic therapy (PDT) efficacy depends on the amount of light distribution within the tissue. However, conventional PDT does not consider the laser irradiation dose during PDT. The optical properties of biological tissues (absorption coefficient μ(a), reduced scattering coefficient μ's), anisotropy factor g, refractive index, etc.) help us to recognize light propagation through the tissue. The goal of this paper is to acquire the knowledge of the light propagation within tissue during and after PDT with the optical property of PDT-performed mouse tumor tissue. The optical properties of mouse tumor tissues were evaluated using a double integrating sphere setup and the algorithm based on the inverse Monte Carlo method in the wavelength range from 350 to 1000 nm. During PDT, the μ(a) and μ's were not changed after 1 and 5 min of irradiation. After PDT, the μ's in the wavelength range from 600 to 1000 nm increased with the passage of time. For seven days after PDT, the μ's increased by 1.7 to 2.0 times, which results in the optical penetration depth decreased by 1.4 to 1.8 times. To ensure an effective procedure, the adjustment of laser parameters for the decreasing penetration depth is recommended for the re-irradiation of PDT.     

In vivo determination of skin near-infrared optical properties using diffuse optical spectroscopy

We develop a superficial diffusing probe with a 3 mm source-detector separation that can be used in combination with diffuse optical spectroscopic (DOS) methods to noninvasively determine full-spectrum optical properties of superficial in vivo skin in the wavelength range from 650 to 1000 nm. This new probe uses a highly scattering layer to diffuse photons emitted from a collimated light source and relies on a two-layer diffusion model to determine tissue absorption coefficient mu a and reduced scattering coefficient mu's. By employing the probe to measure two-layer phantoms that mimic the optical properties of skin, we demonstrate that the probe has an interrogation depth of 1 to 2 mm. We carry out SSFDPM (steady state frequency-domain photon migration) measurements using this new probe on the volar forearm and palm of 15 subjects, including five subjects of African descent, five Asians, and five Caucasians. The optical properties of in vivo skin determined using the superficial diffusing probe show considerable similarity to published optical properties of carefully prepared ex vivo epidermis+dermis.     

Retinoids regulate genes involved in retinoic acid synthesis and transport in human myometrial and fibroid smooth muscle cells

BACKGROUND: Despite the fact that uterine fibroids are the most common benigntumors in women, their etiology is poorly understood. We havepreviously shown that multiple members of the retinoic acid(RA) pathway have altered expression in fibroids compared withnormal myometrium. The aims of the present study were: to investigateregulation of genes involved in the RA pathway in vitro; andto identify genes that can be used as markers to distinguishmyometrial and fibroid smooth muscle cells in culture. METHODS and RESULTS: We demonstrate here for the first time that differential expressionof aldehyde dehydrogenase 1 (ALDH1) between fibroids and myometriumis maintained in cell culture (without endothelial cells), andthat this gene is differentially regulated by retinoids in myometrialcompared with fibroid cells. RA and retinol also regulate expressionof ADH1, cellular retinol binding protein 1 and cellular RAbinding protein 2 in fibroid and myometrial cells. We show thatmany of the RA pathway genes tested maintain expression levelsand differences in vitro. We also identify nine genes that aredifferentially expressed between myometrium and fibroids andmaintain these differences and expression levels in culturedcells isolated from the same tissues. These genes can be usedas markers to distinguish myometrial and fibroid cells in culture. CONCLUSIONS: Based on these findings, we propose that the RA pathway hasan important and possible causative role in fibroid growth,as evidenced by the large number of genes with significantlyaltered expression in uterine fibroids that can be regulatedby RA.     

Gene expression and tissue concentrations of IGF-I in human myometrium and fibroids under different hormonal conditions

The expression of insulin-like growth factor-I (IGF-I) was measured at the mRNA and protein level in myometrium and fibroids from women with and without preoperative treatment with a gonadotrophin-releasing hormone (GnRH) agonist for 3 months, from post-menopausal women, from pregnant women and in myometrium from women without fibroid disease. Women with menstrual periods were classified according to the phase of the cycle. In tissues from non-treated premenopausal women, IGF-I mRNA expression was significantly higher in fibroids than in myometrium, with no differences related to phase of the menstrual cycle. In post-menopausal women and in GnRH agonist-treated women responding to treatment, similar mRNA expression was seen in myometrium and fibroids but the concentrations were lower than in untreated premenopausal women. The IGF-I mRNA value in fibroids from pregnant women was higher than in any other group and myometrium from pregnant women exhibited higher mRNA expression than myometrium from non-treated premenopausal women. The IGF-I protein was more abundant in fibroids than in myometrium of non-treated premenopausal and of pregnant women and in both tissues the concentration was significantly higher in the group of pregnant women. The IGF-I protein concentrations in fibroids and myometrium from GnRH agonist-treated and post-menopausal women were similar to those from premenopausal non-treated women. High sex steroid concentrations in pregnant and non-pregnant women of fertile age seem to be associated with a higher expression of IGF-I in fibroids than in myometrium, suggesting that IGF-I contributes to the selective growth advantage of these tumours.     

The normal human myometrium has a vascular spatial gradient absent in small fibroids

BACKGROUND: The human uterine vasculature is highly structured, exhibiting circumferential and radial branching. Previously published angiograms of the arterial network describe a system of regular coils. Uterine fibroids lack this structured vasculature. In this study, we make a comparison between the vasculature in normal myometrium and in fibroids using robust stereological methods thus far lacking in the literature. METHODS: Stereological and morphometric analysis of the vascular system was carried out on 15 normal and 27 small fibroid (5-40 mm) uteri taken from women suffering menorrhagia. Projected images of published angiograms were also re-examined, measuring tortuosity. RESULTS: A decreasing gradient of vascular smooth muscle from outer to inner myometrium was found in normal uteri, with no corresponding gradient in capillary tissue fraction. An association between vascular luminal size, amplitude and frequency of vessel bending was also established. Conversely, fibroids were found to lack structured or muscularized vasculature. CONCLUSIONS: A quantitative gradient within the myometrial vascular system, which is absent in fibroids, has been demonstrated. These structural differences between diseased and healthy tissues are probably because of differing expression of angiogenic growth factors and may explain the distribution of particles seen after uterine artery embolization.     

Clinical outcomes following percutaneous magnetic resonance image guided laser ablation of symptomatic uterine fibroids

BACKGROUND: Fibroids are common benign tumours of the uterus. Percutaneous magnetic resonance (MR) image guided laser ablation provides a minimally invasive, day-case alternative to surgery for the treatment of symptomatic fibroids. METHODS: Women with symptomatic fibroids wishing to avoid surgery were treated with laser ablation. MR thermal mapping ensured that maximal safe energy was applied. Fibroid volume was measured at 3 and 12 months, menstrual blood loss was recorded before and after treatment and a menorrhagia outcomes questionnaire (MOQ) was used to assess satisfaction. RESULTS: A total of 66 patients was treated. There was a significant (P < 0.001) reduction in mean fibroid volume of 31%. This was 41% at 1 year follow-up (P < 0.001). Measured menstrual blood loss in eight patients complaining of excessive bleeding was reduced (P = 0.012). The MOQ total outcome score was not as good as that seen in hysterectomy patients (P = 0.02) but the quality of life/satisfaction score was similar (P = 0.06). CONCLUSION: We have used objective and subjective outcome measures to determine the efficacy of MR guided laser ablation for fibroids. Based on this limited study we are encouraged that this procedure may represent a minimally invasive alternative therapy for fibroids.     

Differences between the pre-menopausal and post-menopausal uterine fibroid vasculature

OBJECTIVES: To quantitatively examine differences in microvascular density between fibroid and myometrial tissue from fibroid uteri removed at hysterectomy, both before and after the menopause, and with hormone replacement therapy. METHODS: Factor VIII immunostaining of formalin fixed tissues was used to identify blood vessels, and the vessels counted by an investigator blinded to tissue type or menopausal status. RESULTS: The mean myometrial: fibroid MVD ratio was 2.38 higher in the post-menopausal group (95% CI: 0.12, 4.65, p=0.0474) than in the pre-menopausal group, with the hormone therapy (HT)-using post-menopausal group lying in between. An increase in microvascular density in the myometrium after the menopause was responsible for most of the change in ratios seen between the pre and post-menopausal pairs. There was a trend to increasing myometrial MVD with increasing number of years post-menopause. CONCLUSIONS: Myometrial microvascular density increases markedly after the menopause, while fibroid microvascular density does not alter. Thus, the difference between myometrial and fibroid vasculature becomes greater after the menopause. The implications of this for the treatment of fibroids in post-menopausal women is discussed.