Near-infrared spectroscopy has been used for measurement of changes in cerebral Hb concentrations in infants to study cerebral oxygenation and hemodynamics. In this study, measurements by time-resolved spectroscopy (TRS) were performed in 22 neonates to estimate the values of light absorption coefficient and reduced scattering coefficient (' s ), cerebral Hb oxygen saturation (ScO 2 ), cerebral blood volume (CBV), and differential pathlength factor (DPF), and the relationships between postconceptional age and ' s , ScO 2 , CBV, and DPF were investigated. A portable three-wavelength TRS system with a probe attached to the head of the neonate was used. The mean ' s values at 761, 795, and 835 nm in neonates were estimated to be (mean Ϯ SD) 6.46 Ϯ 1.21, 5.90 Ϯ 1.15 and 6.40 Ϯ 1.16/cm, respectively. There was a significant positive relationship between postconceptional age and ' s at those three wavelengths. The mean ScO 2 value was calculated to be 70.0 Ϯ 4.6%, and postconceptional age and ScO 2 showed a negative linear relationship. The mean value of CBV was 2.31 Ϯ 0.56 mL/100 g. There was a significant positive relationship between postconceptional age and CBV. During the perinatal period, the brain undergoes anatomic, functional, and metabolic changes. The anatomic changes include neuronal proliferation, migration, organization, and myelination, and the metabolic changes match the process of initial overproduction and subsequent elimination of excessive neurons, synapses, and dendritic spines known to occur in the developing brain. Noninvasive assessment of cerebral anatomic changes and of oxygen delivery and utilization is useful for evaluating the effectiveness of therapy and for preventing oxygen toxicity in seriously ill neonates.Near-infrared spectroscopy (NIRS) has been used in the clinical field with various measuring devices using several wavelengths. A method using continuous-wave NIRS has been developed and reported to be suitable for clinical use in infants (1-7). However, current commercially available NIRS systems can detect only changes in cerebral Hb. Because NIRS is based on the modified Beer-Lambert law, a change in hematocrit and blood volume as well as developmental and pathophysiologic changes in brain tissue affect the pathlength of near-infrared light. In a few recent studies, absolute values of cerebral Hb oxygen saturation (ScO 2 ) and cerebral blood volume (CBV) in infants were measured without inducing Hb concentration changes by using full-spectral near-infrared spectroscopy (8 -11) and spatially resolved spectroscopy (12). However, these

BACKGROUND Transforming growth factor‐β1 (TGF‐ β1) is a multifunctional factor and is known to affect tumor growth in malignant tumors. The effects of TGF‐β1 on angiogenesis, stromal formation, and immune function suggest its possible involvement in tumor progression. The authors examined whether TGF‐β1 levels may be correlated with angiogenesis, clinicopathologic factors, and survival in patients with surgically resected lung carcinoma. METHODS TGF‐β1 protein was extracted from 53 nonsmall cell lung carcinoma tissue samples (19 squamous cell carcinomas, 33 adenocarcinomas, and 1 adenosquamous cell carcinoma), and its level was measured by enzyme‐linked immunosorbent assay. To assess tumor angiogenesis, microvessel density (MVD) was determined by CD31 immunostaining. RESULTS The protein level of TGF‐β1 was 289 picograms per milligram of protein (pg/mg protein), ranging from 94 pg/mg protein to 584 pg/mg protein. The TGF‐β1 protein level was significantly higher in patients with lymph node metastasis compared with patients who were without lymph node metastasis (P = 0.02), and the TGF‐β1 protein level was significantly higher in patients with Stage III disease (TNM classification) compared with patients who had Stage I and II disease (P = 0.03). There was no significant correlation between the TGF‐β1 protein level and any of the other clinicopathologic factors that were considered. A significant positive correlation between TGF‐β1 protein level and MVD was noted (P < 0.01). Furthermore, in patients with adenocarcinoma, a significant correlation between TGF‐β1 protein level and prognosis was detected by multivariate analysis (P = 0.028). CONCLUSIONS TGF‐β1 seems to affect tumor angiogenesis and to play an important role in tumor progression in patients with nonsmall cell lung carcinoma. Furthermore, the TGF‐β1 protein level may be an independent predictor of survival in patients with adenocarcinoma of the lung. Cancer 2001;91:964–71. © 2001 American Cancer Society.

TGF-beta1 seems to affect tumor angiogenesis and to play an important role in tumor progression in patients with nonsmall cell lung carcinoma. Furthermore, the TGF-beta1 protein level may be an independent predictor of survival in patients with adenocarcinoma of the lung.

During the developmental stage, the brain undergoes anatomic, functional, and metabolic changes necessary to support the complex adaptive behavior of a mature individual. Estimation of developmental changes occurring in different regions of the brain would provide a means of relating various behavioral phenomena to maturation-specific brain structures, thereby providing useful information on structure-function relationships in both normal and disease states. We used multichannel near-infrared spectroscopy (MNIRS), a new noninvasive imaging technique for revealing the course of neural activity in selected brain regions, to monitor the activities of the visual cortex as mirrored by hemodynamic responses in infants subjected to photostimulation during natural sleep. In the infants, oxyhemoglobin and total hemoglobin decreased and deoxyhemoglobin increased in the visual cortex with photostimulation. This pattern of responses was different from the response pattern in adults reported previously. The different patterns of responses to photostimulation in the visual cortices of infants and adults might reflect developmental and behavioral differences. It may reflect a different functional organization of the visual cortex in infants or ongoing retinal development. Our results demonstrated that regional hemodynamic change could be detected in a small area around the visual cortex. MNIRS offers considerable potential for research and noninvasive clinical applications. Hum. Brain Mapp. 22:122-132, 2004.

Near-infrared spectroscopy (NIRS) has been used for measurement of cerebral hemoglobin (Hb) concentrations in neonates to study cerebral oxygenation and hemodynamics. We perform measurements by portable three-wavelength NIR time-resolved spectroscopy (TRS) in a piglet hypoxia model with various degrees of oxygenation to estimate the absorption coefficient (mu(a)) and reduced scattering coefficient (mu(s)') of the head. Measurements of absolute values of mu(a) at three wavelengths enable estimation of Hb concentration and Hb oxygen saturation in the head (SO2). However, there is a problem concerning which background absorption should be used to estimate Hb concentration in the head derived from mu(a) at three wavelengths because it is different from a simple in vitro model. Therefore, we use two different background absorption values with the assumption that background absorption is due only to 85% (by volume) water or that background absorption is equal to absorption of the piglet head with blood exchange transfusion by fluorocarbon (FC), and we compared SO2 measured by TRS with arterial Hb oxygen saturation (SaO2) and sagittal sinus venous Hb oxygen saturation (SvO2) measured by a co-oximeter at several inspired fractional O2(FI(O2)) concentrations. We find that SO2 values using the absorption (abs) of the piglet head with blood exchange transfusion (BET) by FC are not significantly different from SO2 values using the water-only background at FI(O2) in the range of 15 to 100%, but that the values using abs of the head with BET by FC are lower than the values using the water-only background at FI(O2) in the range of 12 to 4%. The SO2 values calculated from the water-only background are higher than those of SaO2 at FI(O2) in the range of 10 to 4%. However, SO2 values using the abs of the head with BET by FC are between those of SaO2 and SvO2 over the whole range of FI(O2). Therefore, abs of the head with BET by FC is more useful for estimation of the absolute values of oxyHb and deoxyHb of the piglet head.

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The heterogeneity of tumor cells is frequently observed in lung cancer, but the clonality of these cells has not yet been established. The distinct components of 12 lung adenosquamous carcinomas were compared by genetic alterations of p53 and K-ras, chromosomal abnormalities at 9p21 and 9q31-32, and immunohistochemical reactions. The immunoreactivity of p53 was consistent in both adenocarcinomatous and squamous cell carcinomatous components as well as in the transitional areas, retaining the morphological characteristics of the distinct components. The same p53 mutation was found in both components of each tumor with p53 overexpression. No K-ras mutations were detected in any of the tumors examined. Three of the four tumors with chromosomal abnormalities detected, one at 9p21 and two at 9q31-32, had coincident abnormalities between the distinct components, whereas one tumor deleted homozygously at 9p21 (D9S259) in the adenocarcinomatous component with loss of heterozygosity in the other component. The expression of squamous cell carcinoma-related antigen in adenocarcinomatous components was significantly higher than that of lung adenocarcinomas (57 +/- 5.8% vs. 1.0 +/- 0.5%, P < 0.0001), whereas Mucin 1 expression is less in these components (9.0 +/- 4.9% vs. 55 +/- 8.2%, P = 0.003). These results suggest monoclonal transition from squamous cell carcinoma to adenocarcinoma in lung adenosquamous carcinoma.