Varsha Jain

MRI Estimation of Global Brain Oxygen Consumption Rate

Measuring the global cerebral metabolic rate of oxygen (CMRO2) is a valuable tool for assessing brain vitality and function. Measurement of blood oxygen saturation (HbO2) and flow in the major cerebral outflow and inflow vessels can provide a global estimate of CMRO2. We demonstrate a rapid noninvasive method for quantifying CMRO2 by simultaneously measuring venous oxygen saturation in the superior sagittal sinus with magnetic resonance susceptometry-based oximetry, a technique that exploits the intrinsic susceptibility of deoxygenated hemoglobin, and the average blood inflow rate with phase-contrast magnetic resonance imaging. The average venous HbO2, cerebral blood flow, and global CMRO2 values in eight healthy, normal study subjects were 64%±4%, 45.2±3.2 mL per 100 g per minute, and 127±7 μmol per 100 g per minute, respectively. These values are in good agreement with those reported in literature. The technique described is noninvasive, robust, and reproducible for in vivo applications, making it ideal for use in clinical settings for assessing the pathologies associated with dysregulation of cerebral metabolism. In addition, the short acquisition time (∼30 seconds) makes the technique suitable for studying the temporal variations in CMRO2 in response to physiologic challenges.

Rapid magnetic resonance measurement of global cerebral metabolic rate of oxygen consumption in humans during rest and hypercapnia

The effect of hypercapnia on cerebral metabolic rate of oxygen consumption (CMRO2) has been a subject of intensive investigation and debate. Most applications of hypercapnia are based on the assumption that a mild increase in partial pressure of carbon dioxide has negligible effect on cerebral metabolism. In this study, we sought to further investigate the vascular and metabolic effects of hypercapnia by simultaneously measuring global venous oxygen saturation (SvO2) and total cerebral blood flow (tCBF), with a temporal resolution of 30 seconds using magnetic resonance susceptometry and phase-contrast techniques in 10 healthy awake adults. While significant increases in SvO2 and tCBF were observed during hypercapnia (P < 0.005), no change in CMRO2 was noted (P > 0.05). Additionally, fractional changes in tCBF and end-tidal carbon dioxide (R2 = 0.72, P < 0.005), as well as baseline SvO2 and tCBF (R2 = 0.72, P < 0.005), were found to be correlated. The data also suggested a correlation between cerebral vascular reactivity (CVR) and baseline tCBF (R2 = 0.44, P = 0.052). A CVR value of 6.1% ± 1.6%/mm Hg was determined using a linear-fit model. Additionally, an average undershoot of 6.7% ± 4% and 17.1% ± 7% was observed in SvO2 and tCBF upon recovery from hypercapnia in six subjects.

Cerebral oxygen metabolism in neonates with congenital heart disease quantified by MRI and optics.

Neonatal congenital heart disease (CHD) is associated with altered cerebral hemodynamics and increased risk of brain injury. Two novel noninvasive techniques, magnetic resonance imaging (MRI) and diffuse optical and correlation spectroscopies (diffuse optical spectroscopy (DOS), diffuse correlation spectroscopy (DCS)), were employed to quantify cerebral blood flow (CBF) and oxygen metabolism (CMRO2) of 32 anesthetized CHD neonates at rest and during hypercapnia. Cerebral venous oxygen saturation (SvO2) and CBF were measured simultaneously with MRI in the superior sagittal sinus, yielding global oxygen extraction fraction (OEF) and global CMRO2 in physiologic units. In addition, microvascular tissue oxygenation (StO2) and indices of microvascular CBF (BFI) and CMRO2 (CMRO2i) in the frontal cortex were determined by DOS/DCS. Median resting-state MRI-measured OEF, CBF, and CMRO2 were 0.38, 9.7 mL/minute per 100 g and 0.52 mL O2/minute per 100 g, respectively. These CBF and CMRO2 values are lower than literature reports for healthy term neonates (which are sparse and quantified using different methods) and resemble values reported for premature infants. Comparison of MRI measurements of global SvO2, CBF, and CMRO2 with corresponding local DOS/DCS measurements demonstrated strong linear correlations (R2=0.69, 0.67, 0.67; P<0.001), permitting calibration of DOS/DCS indices. The results suggest that MRI and optics offer new tools to evaluate cerebral hemodynamics and metabolism in CHD neonates.

Investigating the magnetic susceptibility properties of fresh human blood for noninvasive oxygen saturation quantification

Quantification of blood oxygen saturation on the basis of a measurement of its magnetic susceptibility demands knowledge of the difference in volume susceptibility between fully oxygenated and fully deoxygenated blood (Δχdo). However, two very different values of Δχdo are currently in use. In this work we measured Δχdo as well as the susceptibility of oxygenated blood relative to water, Δχoxy, by MR susceptometry in samples of freshly drawn human blood oxygenated to various levels, from 6 to 98% as determined by blood gas analysis. Regression analysis yielded 0.273 ± 0.006 and −0.008 ± 0.003 ppm (cgs) respectively, for Δχdo and Δχoxy, in excellent agreement with previous work by Spees et al. (Magn Reson Med 2001;45:533–542). Magn Reson Med, 2012.

Longitudinal Reproducibility and Accuracy of Pseudo-Continuous Arterial Spin–labeled Perfusion MR Imaging in Typically Developing Children

PURPOSE To evaluate the longitudinal repeatability and accuracy of cerebral blood flow (CBF) measurements by using pseudo-continuous arterial spin-labeled (pCASL) perfusion magnetic resonance (MR) imaging in typically developing children. MATERIALS AND METHODS Institutional review board approval with HIPAA compliance and informed consent were obtained. Twenty-two children aged 7-17 years underwent repeated pCASL examinations 2-4 weeks apart with a 3-T MR imager, along with in vivo blood T1 and arterial transit time measurements. Phase-contrast (PC) MR imaging was performed as the reference standard for global blood flow volume. Intraclass correlation coefficient (ICC) and within-subject coefficient of variation (wsCV) were used to evaluate accuracy and repeatability. RESULTS The accuracy of pCASL against the reference standard of PC MR imaging increased on incorporating subjectwise in vivo blood T1 measurement (ICC: 0.32 vs 0.58). The ICC further increased to 0.65 by using a population-based model of blood T1. Additionally, CBF measurements with use of pCASL demonstrated a moderate to good level of longitudinal repeatability in whole brain (ICC = 0.61, wsCV = 15%), in gray matter (ICC = 0.65, wsCV = 14%), and across 16 brain regions (mean ICC = 0.55, wsCV = 17%). The mean arterial transit time was 1538 msec ± 123 (standard deviation) in the pediatric cohort studied, which showed an increasing trend with age (P = .043). CONCLUSION Incorporating developmental changes in blood T1 is important for improving the accuracy of pCASL CBF measurements in children and adolescents; the noninvasive nature, accuracy, and longitudinal repeatability should facilitate the use of pCASL perfusion MR imaging in neurodevelopmental studies.

In vivo venous blood T1 measurement using inversion recovery true-FISP in children and adults

A time‐efficient method is described for in vivo venous blood T1 measurement using multiphase inversion‐recovery‐prepared balanced steady‐state free precession imaging. Computer simulations and validation experiments using a flow phantom were carried out to demonstrate the accuracy of the proposed method for measuring blood T1 by taking advantage of the continuous inflow of fresh blood with longitudinal magnetization undisturbed by previous radiofrequency pulses. In vivo measurement of venous blood T1 in the sagittal sinus was carried out in 26 healthy children and adults aged 7–39 years. The measured venous blood T1 values decreased with age as a whole (P = 0.006) and were higher in females than males (P = 0.013), matching the expected developmental changes and gender differences in human hematocrit level. The estimated mean blood T1 values were highly correlated with normal hematocrit levels across age and gender groups (Spearmans r = 0.93, P = 0.008). The longitudinal repeatability of this technique was 4.0% as measured by the within‐subject coefficient of variation. The proposed multiphase inversion recovery‐prepared balanced steady‐state free precession imaging method is a feasible technique for fast (<1 min) and reliable in vivo venous blood T1 measurement and may serve as an index of hematocrit level in individual subjects. Magn Reson Med, 2010.

High temporal resolution MRI quantification of global cerebral metabolic rate of oxygen consumption in response to apneic challenge.

We present a technique for quantifying global cerebral metabolic rate of oxygen consumption (CMRO2) in absolute physiologic units at 3-second temporal resolution and apply the technique to quantify the dynamic CMRO2 response to volitional apnea. Temporal resolution of 3 seconds was achieved via a combination of view sharing and superior sagittal sinus-based estimation of total cerebral blood flow (tCBF) rather than tCBF measurement in the neck arteries. These modifications were first validated in three healthy adults and demonstrated to produce minimal errors in image-derived blood flow and venous oxygen saturation (SvO2) values. The technique was then applied in 10 healthy adults during an apnea paradigm of three repeated 30-second breath-holds. Subject-averaged baseline tCBF, arteriovenous oxygen difference (AVO2D), and CMRO2 were 48.6±7.0 mL/100 g per minute, 29.4 ± 3.4%HbO2, and 125.1±11.4 μmol/100 g per minute, respectively. Subject-averaged maximum changes in tCBF and AVO2D were 43.5±9.4% and − 32.1±5.7%, respectively, resulting in a small (6.0±3.5%) but statistically significant (P = 0.00044, two-tailed t-test) increase in average end-apneic CMRO2. This method could be used to investigate neurometabolic-hemodynamic relationships in normal physiology, to better define the biophysical origins of the BOLD signal, and to quantify neurometabolic responsiveness in diseases of altered neurovascular reactivity.

High temporal resolution in vivo blood oximetry via projection-based T2 measurement

Measuring venous oxygen saturation (HbO2) in large blood vessels can provide important information about oxygen delivery and its consumption in vital organs. Quantification of bloods T2 value via MR can be utilized to determine HbO2 noninvasively. We propose a fast method for in vivo blood T2 quantification via computing the complex difference of velocity‐encoded projections. As blood flows continuously, its signal can be robustly isolated from the surrounding tissue by computing the complex difference of two central k‐space lines with different velocity encodings. This resultant signal can then be measured as a function of echo time for rapidly quantifying T2 of blood. We applied the method to quantify HbO2 in three cerebral veins at rest and in one of the veins in response to hypercapnia. Average HbO2 measurements in superior sagittal sinus (SSS), straight sinus and internal jugular vein in the group were 63 ± 3%, 68 ± 4% and 65 ± 4%, respectively. Average HbO2 values in SSS during baseline, hypercapnia, and recovery were 63 ± 2%, 79 ± 5%, and 61 ± 3%, respectively. When compared with standard T2 quantification techniques, the proposed method is fast, reliable, and robust against partial volume effects. Magn Reson Med 70:785–790, 2013.

Time-resolved Absolute Velocity Quantification with Projections

Quantitative information on time‐resolved blood velocity along the femoral/popliteal artery can provide clinical information on peripheral arterial disease and complement MR angiography as not all stenoses are hemodynamically significant. The key disadvantages of the most widely used approach to time‐resolve pulsatile blood flow by cardiac‐gated velocity‐encoded gradient‐echo imaging are gating errors and long acquisition time. Here, we demonstrate a rapid nontriggered method that quantifies absolute velocity on the basis of phase difference between successive velocity‐encoded projections after selectively removing the background static tissue signal via a reference image. The tissue signal from the reference images center k‐space line is isolated by masking out the vessels in the image domain. The performance of the technique, in terms of reproducibility and agreement with results obtained with conventional phase contrast‐MRI was evaluated at 3 T field strength with a variable‐flow rate phantom and in vivo of the triphasic velocity waveforms at several segments along the femoral and popliteal arteries. Additionally, time‐resolved flow velocity was quantified in five healthy subjects and compared against gated phase contrast‐MRI results. To illustrate clinical feasibility, the proposed method was shown to be able to identify hemodynamic abnormalities and impaired reactivity in a diseased femoral artery. For both phantom and in vivo studies, velocity measurements were within 1.5 cm/s, and the coefficient of variation was less than 5% in an in vivo reproducibility study. In five healthy subjects, the average differences in mean peak velocities and their temporal locations were within 1 cm/s and 10 ms compared to gated phase contrast‐MRI. In conclusion, the proposed method provides temporally resolved arterial velocity with a temporal resolution of 20 ms with minimal post processing. Magn Reson Med, 2010.

Fractionated Stereotactic Radiotherapy for Facial Nerve Schwannomas.

Purpose Data on the clinical course of irradiated facial nerve schwannomas (FNS) are lacking. We evaluated fractionated stereotactic radiotherapy (FSRT) for FNS. Methods Eight consecutive patients with FNS treated at our institution between 1998 and 2011 were included. Patients were treated with FSRT to a median dose of 50.4 Gy (range: 46.8-54 Gy) in 1.8 or 2.0 Gy fractions. We report the radiographic response, symptom control, and toxicity associated with FSRT for FNS. Results The median follow-up time was 43 months (range: 10-75 months). All patients presented with symptoms including pain, tinnitus, facial asymmetry, diplopia, and hearing loss. The median tumor volume was 1.57 cc. On the most recent follow-up imaging, five patients were noted to have stable tumor size; three patients had a net reduction in tumor volume. Additionally, six patients had improvement in clinical symptoms, one patient had stable clinical findings, and one patient had worsened House-Brackmann grade due to cystic degeneration. Conclusion FSRT treatment of FNS results in excellent control of growth and symptoms with a small rate of radiation toxicity. Given the importance of maintaining facial nerve function, FSRT could be considered as a primary management modality for enlarging or symptomatic FNS.