non-invasive-optical-measurement-cerebral-metabolism-hemodynamics

Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants

Perinatal brain injury remains a significant cause of infant mortality  and morbidity, but there is not yet an effective bedside tool that can  accurately ...

Using the delta-P(1) approximation to the Boltzmann transport equation we develop analytic solutions for the fluence rate produced by planar (1-D) and Gaussian beam (2-D) irradiation of a homogeneous, turbid, semi-infinite medium. To assess the performance of these solutions we compare the predictions for the fluence rate and two metrics of the optical penetration depth with Monte Carlo simulations. We provide results under both refractive-index matched and mismatched conditions for optical properties where the ratio of reduced scattering to absorption lies in the range 0< or =(micro(s')/micro(a))< or =10(4). For planar irradiation, the delta-P(1) approximation provides fluence rate profiles accurate to +/-16% for depths up to six transport mean free paths (l*) over the full range of optical properties. Metrics for optical penetration depth are predicted with an accuracy of +/-4%. For Gaussian irradiation using beam radii r(0) > or =3 l*, the accuracy of the fluence rate predictions is no worse than in the planar irradiation case. For smaller beam radii, the predictions degrade significantly. Specifically for media with (micro(s')/micro(a))=1 irradiated with a beam radius of r(0)=l*, the error in the fluence rate approaches 100%. Nevertheless, the accuracy of the optical penetration depth predictions remains excellent for Gaussian beam irradiation, and degrades to only +/-20% for r(0)=l*. These results show that for a given set of optical properties (micro(s')/micro(a)), the optical penetration depth decreases with a reduction in the beam diameter. Graphs are provided to indicate the optical and geometrical conditions under which one must replace the delta-P(1) results for planar irradiation with those for Gaussian beam irradiation to maintain accurate dosimetry predictions.

Radiative transport in the delta-P1 approximation: accuracy of fluence rate and optical penetration depth predictions in turbid semi-infinite media.

We use optical spectroscopy to characterize the influence of mammographic-like compression on the physiology of the breast. We note a reduction in total hemoglobin content, tissue oxygen saturation, and optical scattering under compression. We also note a hyperemic effect during repeated compression cycles. By modeling the time course of the tissue oxygen saturation, we are able to obtain estimates for the volumetric blood flow (1.64+/-0.6 mL/100 mL/min) and the oxygen consumption (1.97+/-0.6 micromol/100 mL/min) of compressed breast tissue. These values are comparable to estimates obtained from previously published positron emission tomography (PET) measurements. We conclude that compression-induced changes in breast physiological properties are significant and should be accounted for when performing optical breast imaging. Additionally, the dynamic characteristics of the changes in breast physiological parameters, together with the ability to probe the tissue metabolic state, may prove useful for breast cancer detection.

Compression-induced changes in the physiological state of the breast as observed through frequency domain photon migration measurements.

We develop algorithms for imaging the time-varying optical absorption within the breast given diffuse optical tomographic data collected over a time span that is long compared to the dynamics of the medium. Multispectral measurements allow for the determination of the time-varying total hemoglobin concentration and of oxygen saturation. To facilitate the image reconstruction, we decompose the hemodynamics in time into a linear combination of spatio-temporal basis functions, the coefficients of which are estimated using all of the data simultaneously, making use of a Newton-based nonlinear optimization algorithm. The solution of the extremely large least-squares problem which arises in computing the Newton update is obtained iteratively using the LSQR algorithm. A Laplacian spatial regularization operator is applied, and, in addition, we make use of temporal regularization which tends to encourage similarity between the images of the spatio-temporal coefficients. Results are shown for an extensive simulation, in which we are able to image and quantify localized changes in both total hemoglobin concentration and oxygen saturation. Finally, a breast compression study has been performed for a normal breast cancer screening subject, using an instrument which allows for highly accurate co-registration of multispectral diffuse optical measurements with an x-ray tomosynthesis image of the breast. We are able to quantify the global return of blood to the breast following compression, and, in addition, localized changes are observed which correspond to the glandular region of the breast.

Spatio-temporal imaging of the hemoglobin in the compressed breast with diffuse optical tomography.

Wir entwickeln die Algorithmen f&uuml;r die zeitlich ver&auml;nderlichen optische Absorption innerhalb der Brust gegeben diffuse optische tomographische Daten gesammelt in einem Zeitraum, der lange verglichen wird auf die Dynamik des Mediums imaging. Multispektrale Messungen zu erm&ouml;glichen, f&uuml;r die Bestimmung von der zeitlich ver&auml;nderlichen insgesamt H&auml;moglobin-Konzentration und der Sauerstoffs&auml;ttigung. Zur Erleichterung der Bildrekonstruktion zerlegen wir die H&auml;modynamik rechtzeitig in eine Linearkombination der r&auml;umlich-zeitliche Grundlage Funktionen, die Koeffizienten von denen gesch&auml;tzt werden alle Daten gleichzeitig verwenden, nutzen eine nichtlineare Optimierung auf der Grundlage der Newton-Algorithmus. Die L&ouml;sung des Problems extrem gro&szlig;e Fehlerquadratmethode die entsteht bei der Berechnung des Newton-Updates wird iterativ mithilfe des LSQR-Algorithmus abgerufen. Ein Laplacian r&auml;umliche Regularisierung Operator angewendet wird, und, dar&uuml;ber hinaus stellen wir der zeitlichen Regularisierung, die tendenziell &Auml;hnlichkeit zwischen den Bildern der raumzeitlichen Koeffizienten verwenden. Ergebnisse sind f&uuml;r eine umfangreiche Simulation, angezeigt, in denen wir in der Lage sind, Bilder und lokalisierte &Auml;nderungen sowohl die Gesamt-H&auml;moglobin-Konzentration als auch die Sauerstoffs&auml;ttigung zu quantifizieren. Schlie&szlig;lich wurde eine Brust-Komprimierung-Studie durchgef&uuml;hrt, f&uuml;r eine normale Brust Krebs Screening Thema, mit einem Instrument die hochgenaue Sensork&ouml;pfe Multispektral diffuse optische Messungen mit einer Tomosynthese R&ouml;ntgenbild der Brust erm&ouml;glicht. Wir sind in der Lage, die globale R&uuml;ckkehr Blut in die Brust nach der Komprimierung zu quantifizieren, und dar&uuml;ber hinaus sind lokalisierte Ver&auml;nderungen beobachtet, die die glandul&auml;re Region der Brust entsprechen.

R&auml;umlich-zeitliche Darstellung der das H&auml;moglobin in der komprimierten Brust mit diffusen optische Tomographie.

We present images of tissue phantoms and chicken chorio-allantoic membrane vasculature using a novel optoacoustic tomography technique based on the time-resolved interferometric measurement of laser-induced thermoelastic expansion. Our imaging system is based on a modified Mach-Zehnder interferometer that provides surface displacement measurements with a temporal resolution of 4 ns and a displacement sensitivity of 0.3 nm. The images are reconstructed from surface displacement measurements made at several locations following irradiation of the sample with Q-switched Nd:YAG (lambda=532, 1064 nm) laser pulses using a delay and sum beam-forming algorithm. The images shown demonstrate the ability of our method to provide better than 200-microm lateral and 30-microm axial resolution at depths exceeding ten transport mean free paths in highly scattering in-vitro and in-vivo model systems.

Optoacoustic imaging based on the interferometric measurement of surface displacement.

In this paper, we report new progress in developing the instrument and software platform of a combined X-ray mammography/diffuse optical breast imaging system. Particularly, we focus on system validation using a series of balloon phantom experiments and the optical image analysis of 49 healthy patients. Using the finite-element method for forward modeling and a regularized Gauss-Newton method for parameter reconstruction, we recovered the inclusions inside the phantom and the hemoglobin images of the human breasts. An enhanced coupling coefficient estimation scheme was also incorporated to improve the accuracy and robustness of the reconstructions. The recovered average total hemoglobin concentration (HbT) and oxygen saturation (SO2) from 68 breast measurements are 16.2 microm and 71%, respectively, where the HbT presents a linear trend with breast density. The low HbT value compared to literature is likely due to the associated mammographic compression. From the spatially co-registered optical/X-ray images, we can identify the chest-wall muscle, fatty tissue, and fibroglandular regions with an average HbT of 20.1+/-6.1 microm for fibroglandular tissue, 15.4+/-5.0 microm for adipose, and 22.2+/-7.3 microm for muscle tissue. The differences between fibroglandular tissue and the corresponding adipose tissue are significant (p < 0.0001). At the same time, we recognize that the optical images are influenced, to a certain extent, by mammographical compression. The optical images from a subset of patients show composite features from both tissue structure and pressure distribution. We present mechanical simulations which further confirm this hypothesis.

Combined optical imaging and mammography of the healthy breast: optical contrast derived from breast structure and compression.

In diesem Beitrag berichten wir &uuml;ber neue Fortschritte bei der Entwicklung der Instrumente und Software-Plattform einer kombinierten R&ouml;ntgen Mammographie/diffuse optische Brust imaging-System. Insbesondere konzentrieren wir uns auf Systemvalidierung, die mit einer Reihe von Ballon-phantom-Experimenten und optische Bildanalyse 49 gesunde Patienten. Mit die Finite-Elemente-Methode f&uuml;r forward-Modellierung und eine regularisierte Gau&szlig;-Newton-Methode f&uuml;r den Parameter Wiederaufbau, erholt wir die Einschl&uuml;sse innerhalb der Phantom und die H&auml;moglobin-Bilder der menschlichen Br&uuml;ste. Eine verst&auml;rkte Kupplung Koeffizient Sch&auml;tzung Regelung wurde auch zur Verbesserung der Genauigkeit und Robustheit der Rekonstruktionen eingegliedert. Die wiederhergestellten durchschnittliche Gesamt-H&auml;moglobin-Konzentration (HbT) und der Sauerstoffs&auml;ttigung (SO2) von 68 Brust Messungen sind 16,2 Microm und 71 %, bzw. wo die HbT &uuml;berreicht einen linearen trend mit Brust-Dichte. Der niedrige HbT-Wert im Vergleich zur Literatur wurde wahrscheinlich durch die zugeordneten Mammographisch Kompression. Aus dem r&auml;umlich mitangemeldeten optische/X-ray Images k&ouml;nnen wir die Brustwand Muskel, Fettgewebe und Fibroglandular Regionen mit einer durchschnittlichen HbT 20.1+/-6.1 Microm f&uuml;r Fibroglandular Gewebe, 15.4+/-5.0 Microm f&uuml;r Fettgewebe und 22.2+/-7.3 Microm f&uuml;r Muskelgewebe identifizieren. Die Unterschiede zwischen Fibroglandular Gewebe und entsprechende Fettgewebe sind bedeutende (p &lt; 0,0001). Zur gleichen Zeit erkennen wir, dass die optische Bilder, bis zu einem gewissen Grad von mammographical Kompression beeinflusst werden. Die optische Bilder aus einer Teilmenge von Patienten zeigen zusammengesetzte Funktionen aus beiden Gewebe Struktur und Druck-Verteilung. Wir pr&auml;sentieren die mechanische Simulationen, die weitere diese Hypothese zu best&auml;tigen.

Kombinierte optische Bildgebung und Mammographie der gesunden Brust: Optischer Kontrast von Brust-Struktur und Kompression abgeleitet.

Mit den Ursachen der perinatalen Gehirn Verletzungen noch unklar und die wahrscheinliche Rolle der h&auml;modynamischen Instabilit&auml;t in ihrer &Auml;tiologie Schreibmappe &Uuml;berwachung der neonatale zerebrale H&auml;modynamik mit standard-Werten als Funktion des Alters sind erforderlich. In dieser Studie haben wir kombiniert quantitative Frequenzbereich nahe Infrarotspektroskopie (FD-NIRS) Ma&szlig;nahmen der zerebralen Gewebe mit Sauerstoff (StO(2)) und zerebrale Blutvolumen (CBV) mit Verbreitung Korrelation Spektroskopie (DCS) Ma&szlig;nahmen eines zerebralen Blut flie&szlig;en Index (CBF(ix)), um die G&uuml;ltigkeit der CBV-CBF-Beziehung bei vorzeitigen Neugeborenen zu testen und sch&auml;tzen zerebralen Stoffwechsel Sauerstoff (rCMRO(2)) mit oder ohne die CBF(ix)-Messung. Wir messen 11 vorzeitige Neugeborene (28-34 Wochen Gestationsalter) ohne bekannte neurologische Probleme, einmal pro Woche ein bis sechs Wochen alt. Bei 9 Patienten zerebralen Blut Geschwindigkeiten von der mittleren Hirnarterie durch Transkranielle Doppler (TCD) gesammelt und mit DCS-Werten verglichen. Ergebnisse zeigen einen stetigen R&uuml;ckgang der StO(2) in den ersten sechs Wochen des Lebens w&auml;hrend CBV stabil bleiben und eine stetige Steigerung der CBF(ix). rCMRO(2) gesch&auml;tzt von FD-NIRS breiten interindividuellen Variabilit&auml;t zeigt aber konstant bleibt. rCMRO(2) ergibt sich aus FD-NIRS und DCS kombiniert um 40 % in den ersten sechs Wochen des Lebens mit geringeren interindividuellen Variabilit&auml;t. TCD und DCS-Werte sind positiv korreliert. Abschlie&szlig;end bietet FD-NIRS kombiniert mit DCS eine quantitative Schreibmappe Methode zur Bewertung von CBV, StO(2), CBF und rCMRO(2) im vorzeitigen Gehirn, individuelle Begleitung und Vergleich zwischen Patienten zu erleichtern. Eine stabile CBV-CBF-Beziehung darf verfr&uuml;ht Neugeborenen nicht.

Nicht-invasive optische Ma&szlig;nahmen CBV, StO(2), CBF Index und rCMRO(2) in den Gehirnen der menschlichen vorzeitige Neugeborene in den ersten sechs Wochen des Lebens.

With the causes of perinatal brain injuries still unclear and the probable role of hemodynamic instability in their etiology, bedside monitoring of neonatal cerebral hemodynamics with standard values as a function of age are needed. In this study, we combined quantitative frequency domain near infrared spectroscopy (FD-NIRS) measures of cerebral tissue oxygenation (StO(2)) and cerebral blood volume (CBV) with diffusion correlation spectroscopy (DCS) measures of a cerebral blood flow index (CBF(ix)) to test the validity of the CBV-CBF relationship in premature neonates and to estimate cerebral metabolic rate of oxygen (rCMRO(2)) with or without the CBF(ix) measurement. We measured 11 premature neonates (28-34 weeks gestational age) without known neurological issues, once a week from one to six weeks of age. In nine patients, cerebral blood velocities from the middle cerebral artery were collected by transcranial Doppler (TCD) and compared with DCS values. Results show a steady decrease in StO(2) during the first six weeks of life while CBV remains stable, and a steady increase in CBF(ix). rCMRO(2) estimated from FD-NIRS remains constant but shows wide interindividual variability. rCMRO(2) calculated from FD-NIRS and DCS combined increased by 40% during the first six weeks of life with reduced interindividual variability. TCD and DCS values are positively correlated. In conclusion, FD-NIRS combined with DCS offers a safe and quantitative bedside method to assess CBV, StO(2), CBF, and rCMRO(2) in the premature brain, facilitating individual follow-up and comparison among patients. A stable CBV-CBF relationship may not be valid for premature neonates.

Noninvasive optical measures of CBV, StO(2), CBF index, and rCMRO(2) in human premature neonates' brains in the first six weeks of life.

To date, the majority of neurovascular coupling studies focused on the thalamic afferents' activity in layer IV and the corresponding large spiking activity as responsible for functional hyperemia. This paper highlights the role of the secondary and late cortico-cortical transmission in neurovascular coupling. Simultaneous scalp electroencephalography (EEG) and diffuse optical imaging (DOI) measurements were obtained during multiple conditions of event-related electrical forepaw stimulation in 33 male Sprague-Dawley rats divided into 6 groups depending on the maintaining anesthetic - alpha-chloralose, pentobarbital, ketamine-xylazine, fentanyl-droperidol, isoflurane, or propofol. The somatosensory evoked potentials (SEP) were decomposed into four components and the question of which best predicts the hemodynamic responses was investigated. Results of the linear regression analysis show that the hemodynamic response is best correlated with the secondary and late cortico-cortical transmissions and not with the initial thalamic input activity in layer IV. Baseline cerebral blood flow (CBF) interacts with neural activity and influences the evoked hemodynamic responses. Finally, neurovascular coupling appears to be the same across all anesthetics used.

The effect of different anesthetics on neurovascular coupling.

Bis heute ist die Mehrheit der Neurovaskul&auml;re Schwerpunkt Kupplung Studien den thalamischen afferenten T&auml;tigkeit in Schicht IV und der entsprechenden gro&szlig;en Blindkontrollen Aktivit&auml;t als verantwortlich f&uuml;r die funktionelle Hyper&auml;mie. Dieses Papier unterstreicht die Rolle der Sekund&auml;r- und sp&auml;ten Kortikosteroide-kortikale &Uuml;bertragung in Neurovaskul&auml;re Kopplung. Gleichzeitige Kopfhaut Elektroenzephalographie (EEG) und diffuse optische Bildgebung (DOI)-Messungen wurden w&auml;hrend mehrerer Bedingungen der ereignisbezogene elektrische Forepaw Stimulation in 33 m&auml;nnliche Sprague-Dawley Ratten eingeteilt in 6 Gruppen je nach der Pflege An&auml;sthetikum - Alpha-Chloralose, Pentobarbital, Ketamin-Xylazin, Fentanyl-Droperidol, Isofluran oder Propofol erzielt. Die somatosensorische evozierte Potentiale (SEP) wurden in vier Komponenten zerlegen und die Frage, von der am besten die h&auml;modynamischen Reaktionen prognostiziert, wurde untersucht. Ergebnisse der linearen Regressionsanalyse zeigen, dass die h&auml;modynamische Antwort am besten mit der Sekund&auml;r- und sp&auml;ten Kortikosteroide-kortikalen getrieben und nicht mit der urspr&uuml;nglichen thalamischen Eingang Aktivit&auml;t in Schicht IV korreliert ist. Grundlinie zerebralen Blutflusses (CBF) interagiert mit neuronalen Aktivit&auml;t und beeinflusst die evozierten h&auml;modynamischen Reaktionen. Schlie&szlig;lich scheint Neurovaskul&auml;re Kopplung auf alle An&auml;sthetika verwendet identisch sein.

Die Wirkung der verschiedenen An&auml;sthetika auf Neurovaskul&auml;re Kopplung.

To explore the optical and physiologic properties of normal and lesion-bearing breasts by using a combined optical and digital breast tomosynthesis (DBT) imaging system.

Combined optical and X-ray tomosynthesis breast imaging.

Die optischen und physiologischen Eigenschaften von normalen und L&auml;sion-Lager Br&uuml;ste erkunden mit einer kombinierten optischen und digitalen Brust Tomosynthese (DBT) imaging-System.

Kombinierte optische und x-ray Tomosynthese Brustkrebs Bildgebung.

Laser Speckle Imaging (LSI) images interference patterns produced by coherent addition of scattered laser light to map subsurface tissue perfusion. However, the effect of longer path length photons is typically unknown and poses a limitation towards absolute quantification. In this work, LSI is integrated with spatial frequency domain imaging (SFDI) to suppress multiple scattering and absorption effects. First, depth sensitive speckle contrast is shown in phantoms by separating a deep source (4 mm) from a shallow source (2 mm) of speckle contrast by using a high spatial frequency of illumination (0.24 mm(-1)). We develop an SFD adapted correlation diffusion model and show that with high frequency (0.24 mm(-1)) illumination, doubling of absorption contrast results in only a 1% change in speckle contrast versus 25% change using a planar unmodulated (0 mm(-1)) illumination. Similar absorption change is mimicked in vivo imaging a finger occlusion and the relative speckle contrast change from baseline is 10% at 0.26 mm(-1) versus 60% at 0 mm(-1) during a finger occlusion. These results underscore the importance of path length and optical properties in determining speckle contrast. They provide an integrated approach for simultaneous mapping of blood flow (speckle contrast) and oxygenation (optical properties) which can be used to inform tissue metabolism.

Laser speckle imaging in the spatial frequency domain.

Laser-Speckle-Imaging (LSI) Bilder Interferenzmuster produziert durch koh&auml;rente Addition von zerstreuten Laserlicht Untergrund Gewebe Perfusion zuordnen. Jedoch wird der Effekt l&auml;nger Weg L&auml;nge Photonen ist in der Regel nicht bekannt und stellt eine Einschr&auml;nkung in Richtung absolute Quantifizierung. In dieser Arbeit ist LSI imaging (SFDI), um mehrere Effekte von Streuung und Absorption zu unterdr&uuml;cken r&auml;umliche Frequenz-Dom&auml;ne integriert. Zun&auml;chst tiefe sensible Speckle Kontrast Phantome zeigt durch die Trennung einer tiefen Quelle (4 mm) aus einer flachen (2 mm) der Speckle-Kontrast mit eine hohe r&auml;umliche Frequenz der Beleuchtung (0,24 mm(-1)). Wir entwickeln ein SFD angepasst Korrelation-Diffusionsmodell und zeigen, dass mit hoher Frequenz (0,24 mm(-1)) Beleuchtung, Verdoppelung der Resorption Kontrast Ergebnisse nur eine 1 % Ver&auml;nderung Speckle Kontrast im Vergleich zu 25 % Ver&auml;nderung mit einer planaren unmodulated (0 mm(-1)) Beleuchtung. &Auml;hnliche Resorption Ver&auml;nderung ist nachgeahmt in-vivo imaging eine Finger-Okklusion und der relativen Speckle Kontrast &auml;ndert von Baseline ist 10 % bei 0,26 mm(-1) gegen&uuml;ber 60 % bei 0 mm(-1) w&auml;hrend ein Finger-Okklusion. Diese Ergebnisse unterstreichen die Bedeutung der Wegl&auml;nge und optischen Eigenschaften bei der Bestimmung der Speckle-Kontrast. Sie bieten ein integriertes Konzept f&uuml;r die gleichzeitige Zuordnung des Blutflusses (Speckle Kontrast) und Sauerstoffversorgung (optische Eigenschaften), die verwendet werden k&ouml;nnen, um Gewebe Stoffwechsel zu informieren.

Laser-Speckle-Bildgebung in der r&auml;umliche Frequenz-Dom&auml;ne.

We suggest that Diffuse Correlation Spectroscopy (DCS) measurements of tissue blood flow primarily probe relative red blood cell (RBC) motion, due to the occurrence of multiple sequential scattering events within blood vessels. The magnitude of RBC shear-induced diffusion is known to correlate with flow velocity, explaining previous reports of linear scaling of the DCS "blood flow index" with tissue perfusion despite the observed diffusion-like auto-correlation decay. Further, by modeling RBC mean square displacement using a formulation that captures the transition from ballistic to diffusive motion, we improve the fit to experimental data and recover effective diffusion coefficients and velocity de-correlation time scales in the range expected from previous blood rheology studies.

Due to intravascular multiple sequential scattering, Diffuse Correlation Spectroscopy of tissue primarily measures relative red blood cell motion within vessels.

Wir empfehlen, dass Diffuse Correlation Spectroscopy (DCS) Messungen der Gewebe Blut in erster Linie Sonde relative Red Blood Cell (RBC) Bewegung, durch das Auftreten von mehreren sequenziellen Streuung Ereignissen innerhalb der Blutgef&auml;&szlig;e flie&szlig;en. Das Ausma&szlig; der RBC induziert durch Scherung Diffusion ist bekannt, dass mit Str&ouml;mungsgeschwindigkeit, fr&uuml;here Berichte von linearen Skalierung der DCS &quot;Blut Flow Index&quot; zu erkl&auml;ren mit Gewebe Perfusion trotz des Zerfalls festgestellte Verbreitung-wie Auto-Korrelation zu korrelieren. Des weiteren durch modellieren RBC mittlere quadratische Verschiebung mit eine Formulierung, die den &Uuml;bergang von ballistischen diffusiven Bewegung erfasst, wir verbessern an experimentelle Daten anpassen und effektiven Diffusionskoeffizienten und Geschwindigkeit Dekorrelation Zeitskalen in der Erwartungen von fr&uuml;heren Blut Rheologie Studien zu erholen.

Durch intravaskul&auml;re misst mehrere sequenzielle Streuung, Diffuse Korrelation Spektroskopie des Gewebes vor allem relative roter Blutk&ouml;rperchen Bewegung innerhalb der Schiffe.

Little is known about cerebral blood flow, cerebral blood volume (CBV), oxygenation, and oxygen consumption in the premature newborn brain. We combined quantitative frequency-domain near-infrared spectroscopy measures of cerebral hemoglobin oxygenation (SO(2)) and CBV with diffusion correlation spectroscopy measures of cerebral blood flow index (BF(ix)) to determine the relationship between these measures, gestational age at birth (GA), and chronological age. We followed 56 neonates of various GA once a week during their hospital stay. We provide absolute values of SO(2) and CBV, relative values of BF(ix), and relative cerebral metabolic rate of oxygen (rCMRO(2)) as a function of postmenstrual age (PMA) and chronological age for four GA groups. SO(2) correlates with chronological age (r=-0.54, P value â‰¤0.001) but not with PMA (r=-0.07), whereas BF(ix) and rCMRO(2) correlate better with PMA (r=0.37 and 0.43, respectively, P value â‰¤0.001). Relative CMRO2 during the first month of life is lower when GA is lower. Blood flow index and rCMRO(2) are more accurate biomarkers of the brain development than SO(2) in the premature newborns.

Near-infrared spectroscopy assessment of cerebral oxygen metabolism in the developing premature brain.

The hemodynamic functional response is used as a reliable marker of neuronal activity in countless studies of brain function and cognition. In newborns and infants, however, conflicting results have appeared in the literature concerning the typical response, and there is little information on brain metabolism and functional activation. Measurement of all hemodynamic components and oxygen metabolism is critical for understanding neurovascular coupling in the developing brain. To this end, we combined multiple near infrared spectroscopy techniques to measure oxy- and deoxy-hemoglobin concentrations, cerebral blood volume (CBV), and relative cerebral blood flow (CBF) in the somatosensory cortex of 6 preterm neonates during passive tactile stimulation of the hand. By combining these measures we estimated relative changes in the cerebral metabolic rate of oxygen consumption (rCMRO(2)). CBF starts increasing immediately after stimulus onset, and returns to baseline before blood volume. This is consistent with the model of pre-capillary arteriole active dilation driving the CBF response, with a subsequent CBV increase influenced by capillaries and veins dilating passively to accommodate the extra blood. rCMRO(2) estimated using the steady-state formulation shows a biphasic pattern: an increase immediately after stimulus onset, followed by a post-stimulus undershoot due to blood flow returning faster to baseline than oxygenation. However, assuming a longer mean transit time from the arterial to the venous compartment, due to the immature vascular system of premature infants, reduces the post-stimulus undershoot and increases the flow/consumption ratio to values closer to adult values reported in the literature. We are the first to report changes in local rCBF and rCMRO(2) during functional activation in preterm infants. The ability to measure these variables in addition to hemoglobin concentration changes is critical for understanding neurovascular coupling in the developing brain, and for using this coupling as a reliable functional imaging marker in neonates.

Article	Year
Radiative transport in the delta-P1 approximation: accuracy of fluence rate and optical penetration depth predictions in turbid semi-infinite media. Journal of biomedical optics\| PubMed ID: 15189103	2004
Compression-induced changes in the physiological state of the breast as observed through frequency domain photon migration measurements. Journal of biomedical optics\| PubMed ID: 17212539	2006
Spatio-temporal imaging of the hemoglobin in the compressed breast with diffuse optical tomography. Physics in medicine and biology\| PubMed ID: 17664563	2007
Optoacoustic imaging based on the interferometric measurement of surface displacement. Journal of biomedical optics\| PubMed ID: 18163817	2007
Combined optical imaging and mammography of the healthy breast: optical contrast derived from breast structure and compression. IEEE transactions on medical imaging\| PubMed ID: 19116186	2009
Noninvasive optical measures of CBV, StO(2), CBF index, and rCMRO(2) in human premature neonates' brains in the first six weeks of life. Human brain mapping\| PubMed ID: 19650140	2010
The effect of different anesthetics on neurovascular coupling. NeuroImage\| PubMed ID: 20350606	2010
Combined optical and X-ray tomosynthesis breast imaging. Radiology\| PubMed ID: 21062924	2011
Laser speckle imaging in the spatial frequency domain. Biomedical optics express\| PubMed ID: 21698018	2011
Due to intravascular multiple sequential scattering, Diffuse Correlation Spectroscopy of tissue primarily measures relative red blood cell motion within vessels. Biomedical optics express\| PubMed ID: 21750779	2011
Near-infrared spectroscopy assessment of cerebral oxygen metabolism in the developing premature brain. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism\| PubMed ID: 22027937	2012
Somatosensory evoked changes in cerebral oxygen consumption measured non-invasively in premature neonates. NeuroImage\| PubMed ID: 23370052	2013

Stefan Carp

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