Quantitative magnetization transfer (qMT) imaging yields indices describing the interactions between free water protons and immobile macromolecular protons. These indices include the macromolecular to free pool size ratio (PSR), which has been shown to be correlated with myelin content in white matter. Because of the long scan times required for whole-brain imaging (≈20–30 min), qMT studies of the human brain have not found widespread application. Herein, we investigated whether the increased signal-to-noise ratio available at 7.0 T could be used to reduce qMT scan times. More specifically, we developed a selective inversion recovery (SIR) qMT imaging protocol with a i) novel transmit radiofrequency (B1+) and static field (B0) insensitive inversion pulse, ii) turbo field-echo readout, and iii) reduced TR. In vivo qMT data were obtained in the brains of healthy volunteers at 7.0 T using the resulting protocol (scan time≈40 s/slice, resolution=2×2×3 mm3). Reliability was also assessed in repeated acquisitions. The results of this study demonstrate that SIR qMT imaging can be reliably performed within the radiofrequency power restrictions present at 7.0 T, even in the presence of large B1+ and B0 inhomogeneities. Consistent with qMT studies at lower field strengths, the observed PSR values were higher in white matter (mean±SD=17.6±1.3%) relative to gray matter (10.3±1.6%) at 7.0 T. In addition, regional variations in PSR were observed in white matter. Together, these results suggest that qMT measurements are feasible at 7.0 T and may eventually allow for the high-resolution assessment of changes in composition throughout the normal and diseased human brain in vivo.

Background: Due to changes in guidelines and access to treatment, more children start combination antiretroviral therapy (ART) in infancy. With few studies examining the long-term effects of perinatal HIV infection and early ART on neurodevelopment, much is still unknown about brain maturation in the presence of HIV and ART. Follow-up studies of HIV infected (HIV+) children are important for monitoring brain development in the presence of HIV infection and ART.Methods: We use diffusion tensor imaging (DTI) to examine white matter (WM) in 65 HIV+ and 46 control (HIV exposed uninfected (HEU) and HIV unexposed uninfected (HU)) 7-year-old children. This is a follow up of a cohort studied at 5 years, where we previously reported lower fractional anisotropy (FA) in corticospinal tract (CST) and mean diffusivity (MD) increases in inferior/superior longitudinal fasciculi (ILF/SLF), inferior fronto-occipital fasciculus (IFOF) and uncinate fasciculus (UF) in HIV+ children compared to uninfected controls. In addition, we also found a difference in FA related to age at which ART was initiated.Results: At 7 years, we found two regions in the left IFOF and left ILF with lower FA in HIV+ children compared to controls. Higher MD was observed in a similar region in the IFOF, albeit bilaterally, as well as multiple clusters bilaterally in the superior corona radiata (SCR), the anterior thalamic radiation (ATR) and the right forceps minor. Unlike at 5 years, we found no impact on WM of ART initiation. In HEU children, we found a cluster in the right posterior corona radiata with higher FA compared to HU children, while bilateral regions in the CST demonstrated reduced MD.Conclusions: At age 7, despite early ART and viral load (VL) suppression, we continue to observe differences in WM integrity. WM damage observed at age 5 years persists, and new damage is evident. The continued observation of regions with lower FA and higher MD in HIV+ children point to disruptions in ongoing white matter development regardless of early ART. Lastly, in HEU children we find higher FA and lower MD in clusters in the CST tract suggesting that perinatal HIV/ART exposure has a long-term impact on WM development.

A new class of composite RF pulses that perform well in the presence of specific ranges of B 0 and inhomogeneities has been designed for volume (non-selective) excitation in MRI. The pulses consist of numerous (~ 100) short (~ 10µs) block-shaped sub-pulses each with different phases and amplitudes derived from numerical optimization. Optimized pulses are designed to be effective over a specific range of frequency offsets and transmit field variations and are thus implementable regardless of field strength, transmit coil configuration, or the subject-specific spatial distribution of the static and RF fields. In the context of 7T human brain imaging, both simulations and phantom experiments indicate that optimized pulses result in similar on-resonance flip-angle uniformity as BIR-4 pulses but with the advantages of superior off-resonance stability and significantly reduced average power. The pulse design techniques presented here are thus well-suited for practical application in ultra-high field human MRI.

Organ development requires the integration of multiple extracellular signals to assure a proper balance between proliferation and differentiation and to achieve and maintain specialized functions. Considerable progress has been made in the study of hormones and growth factors and in the understanding of the regulated intracellular pathways and transcriptional events that contribute to mammogenesis. Cell culture experiments have pointed out crucial pathways and components, which were subsequently validated in vivo experiments. We found that the mammalian target of rapamycin (mTOR) pathway is essential for both growth and differentiation of mammary epithelial cells and that the action of mTOR is mediated through the induction of the helix-loop-helix transcriptional regulators Id1 and Id2. Pharmacological inhibition of mTOR activity in HC11 mammary epithelial cells reduced cellular proliferation and prevented the lactogenic hormone-induced expression of milk proteins. Treatment of female mice with rapamycin impaired mammary gland differentiation and milk protein synthesis. The effects of mTOR on proliferation and differentiation require the functions of the helix-loop-helix proteins Id1 and Id2. Rapamycin treatment of HC11 cells resulted in a suppression of Id1 expression and an inhibition of proliferation. This effect of rapamycin was reversed by the forced expression of Id1. Rapamycin also prevented the induction of Id2 by lactogenic hormones and milk protein gene expression. Expression of a Id2 transgene bypassed the requirement of mTOR activity for beta-casein induction. These data suggest that mTOR activity has distinguishable functions in the proliferative and the differentiated state of mammary epithelial cells: it is a prerequisite for proliferation through the induction of Id1 and for differentiation-specific gene expression through the induction of Id2. The relative strengths of these proliferation and differentiation signals reflected by the expression levels of the individual Id proteins are crucial to the functional life cycle of mammary epithelial cells and might be disturbed in tumorigenesis.

There is a continuing need for improved RF pulses that achieve proper refocusing in the context of ultra-high field (≥ 7 T) human MRI. Simple block or sinc pulses are highly susceptible to RF field inhomogeneities, and adiabatic pulses are generally considered too SAR intensive for practical use at 7 T. The performance of the array of pulses falling between these extremes, however, has not been systematically evaluated. The aim of this work was to compare the performances of 21 non-selective refocusing pulses spanning a range of durations and SAR levels. The evaluation was based upon simulations and both phantom and in vivo human brain experiments conducted at 7 T. Tested refocusing designs included block, composite block, BIR-4, hyperbolic secant, and numerically optimized composite waveforms. These pulses were divided into three SAR classes and two duration categories, and, based on signal gain in a 3-D spin echo sequence, practical recommendations on usage are made within each category. All evaluated pulses were found to produce greater volume-averaged signals relative to a 180° block pulse. Although signal gains often come with the price of increased SAR or duration, some pulses were found to result in significant signal enhancement while also adhering to practical constraints. This work demonstrates the signal gains and losses realizable with single-channel refocusing pulse designs and should assist in the selection of suitable refocusing pulses for practical 3-D spin-echo imaging at 7 T. It further establishes a reference against which future pulses and multi-channel designs can be compared.