We have used an intensity modulated optical spectrometer, which measures the phase shift across tissue experienced by intensity modulated near-infrared light, to determine the absolute optical pathlength through tissue. The instrument is portable and takes only 5 s to record pathlength at four wavelengths (690 nm, 744 nm, 807 nm and 832 nm). The absolute pathlength divided by the known spacing between the light source and detector on the skin is the differential pathlength factor (DPF) which previous studies have shown is approximately constant for spacings greater than 2.5 cm. DPF results are presented for measurements on 100 adults and 35 newborn infants to determine the statistical variation on the DPF. All measurements were made at a frequency of 200 MHz with source-detector spacings of > 4 cm. Results at 807 nm show a DPF of 4.16(+/- 18.8%) for adult arm, 5.51(+/- 18%) for adult leg, 6.26(+/- 14.1%) for adult head and 4.99(+/- 9%) for the head of a newborn infant. A wavelength dependence was obtained for DPF on all tissues and a difference in DPF between male and female was observed for both the adult arm and leg. The results can be used to improve the quantitation of chromophore concentration changes in adults and newborn infants.

Near infrared spectroscopy (NIRS) has been used to measure concentration changes of cerebral hemoglobin and cytochrome in neonates, children, and adults, to study cerebral oxygenation and hemodynamics. To derive quantitative concentration changes from measurements of light attenuation, the optical path length must be known. This is obtained by multiplying the source/ detector separation by a laboratory measured differential path length factor (DPF) which accounts for the increased distance traveled by light due to scattering. DPF has been measured by time of flight techniques on small populations of adults and postmortem infants. The values for adults are greater than those for newborns, and it is not clear how to interpolate the present data for studies on children. Recent developments in instrumentation using phase resolved spectroscopy techniques have produced a bedside unit which can measure optical path length on any subject. We have developed an intensity modulated optical spectrometer which measures path length at four wavelengths. Two hundred and eighty three subjects from 1 d of age to 50 y were studied. Measurements were made at a fixed frequency of 200 MHz and a source detector separation of 4.5 cm. Results suggest a slowly varying age dependence of DPF, following the relation DPF690 = 5.38 + 0.049A0.877, DPF744 = 5.11 + 0.106A0.723, DPF807 = 4.99 + 0.067A0.814, and DPF832 = 4.67 + 0.062A0.819, where DPF690 is the DPF measured at 690 nm and A is age is expressed in years from full term. There was a wide scatter of values, however, implying that ideally DPF should be measured at the time of each study.

There was a trend for the IR-TSE sequence to underestimate T1 in vivo. The sequence parameters for the IR-TSE and MPRAGE sequences were also optimized in terms of the signal-to-noise ratio (SNR) in the fitted T1. The optimal sequence for IR-TSE in terms of SNR in the fitted T1 was found to have five readouts at TIs of 120, 260, 563, 1,221, 2,647, 5,736 ms and TR of 7 s. The optimal pulse sequence for MPRAGE with readout flip angle = 8 degrees was found to have five readouts at TIs of 160, 398, 988, 2,455, and 6,102 ms and a TR of 9 s. Further optimization including the readout flip angle suggests that the flip angle should be increased, beyond levels that are acceptable in terms of power deposition and point-spread function.

Different MRI techniques are used to investigate multiple sclerosis (MS) in vivo. The pathological specificity of these techniques is poorly understood, in particular their relationship to demyelination and axonal loss. The aim of this study was to evaluate the pathological substrate of high field MRI in post-mortem (PM) spinal cord (SC) of patients with MS. MRI was performed in PMSCs of four MS patients and a healthy subject on a 7 Tesla machine. Quantitative MRI maps (PD; T2; T1; magnetization transfer ratio, MTR; diffusion weighted imaging) were obtained. After scanning, the myelin content and the axonal density of the specimens were evaluated neuropathologically using quantitative techniques. Myelin content and axonal density correlated strongly with MTR, T1, PD, and diffusion anisotropy, but only moderately with T2 and weakly with the apparent diffusion coefficient. Quantitative MR measures provide a promising tool to evaluate components of MS pathology that are clinically meaningful. Further studies are warranted to investigate the potential of new quantitative MR measures to enable a distinction between axonal loss and demyelination and between demyelinated and remyelinated lesions.

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