L. Tugan Muftuler

Children's Brain Development Benefits from Longer Gestation.

Disruptions to brain development associated with shortened gestation place individuals at risk for the development of behavioral and psychological dysfunction throughout the lifespan. The purpose of the present study was to determine if the benefit for brain development conferred by increased gestational length exists on a continuum across the gestational age spectrum among healthy children with a stable neonatal course. Neurodevelopment was evaluated with structural magnetic resonance imaging in 100 healthy right-handed 6- to 10-year-old children born between 28 and 41 gestational weeks with a stable neonatal course. Data indicate that a longer gestational period confers an advantage for neurodevelopment. Longer duration of gestation was associated with region-specific increases in gray matter density. Further, the benefit of longer gestation for brain development was present even when only children born full term were considered. These findings demonstrate that even modest decreases in the duration of gestation can exert profound and lasting effects on neurodevelopment for both term and preterm infants and may contribute to long-term risk for health and disease.

High pregnancy anxiety during mid-gestation is associated with decreased gray matter density in 6-9-year-old children.

Because the brain undergoes dramatic changes during fetal development it is vulnerable to environmental insults. There is evidence that maternal stress and anxiety during pregnancy influences birth outcome but there are no studies that have evaluated the influence of stress during human pregnancy on brain morphology. In the current prospective longitudinal study we included 35 women for whom serial data on pregnancy anxiety was available at 19 (+/-0.83), 25 (+/-0.9) and 31 (+/-0.9) weeks gestation. When the offspring from the target pregnancy were between 6 and 9 years of age, their neurodevelopmental stage was assessed by a structural MRI scan. With the application of voxel-based morphometry, we found regional reductions in gray matter density in association with pregnancy anxiety after controlling for total gray matter volume, age, gestational age at birth, handedness and postpartum perceived stress. Specifically, independent of postnatal stress, pregnancy anxiety at 19 weeks gestation was associated with gray matter volume reductions in the prefrontal cortex, the premotor cortex, the medial temporal lobe, the lateral temporal cortex, the postcentral gyrus as well as the cerebellum extending to the middle occipital gyrus and the fusiform gyrus. High pregnancy anxiety at 25 and 31 weeks gestation was not significantly associated with local reductions in gray matter volume.This is the first prospective study to show that a specific temporal pattern of pregnancy anxiety is related to specific changes in brain morphology. Altered gray matter volume in brain regions affected by prenatal maternal anxiety may render the developing individual more vulnerable to neurodevelopmental and psychiatric disorders as well as cognitive and intellectual impairment.

Distinct pattern separation related transfer functions in human CA3/dentate and CA1 revealed using high-resolution fMRI and variable mnemonic similarity

Producing and maintaining distinct (orthogonal) neural representations for similar events is critical to avoiding interference in long-term memory. Recently, our laboratory provided the first evidence for separation-like signals in the human CA3/dentate. Here, we extended this by parametrically varying the change in input (similarity) while monitoring CA1 and CA3/dentate for separation and completion-like signals using high-resolution fMRI. In the CA1, activity varied in a graded fashion in response to increases in the change in input. In contrast, the CA3/dentate showed a stepwise transfer function that was highly sensitive to small changes in input.

Ultrahigh-resolution microstructural diffusion tensor imaging reveals perforant path degradation in aged humans in vivo

The perforant path (PP) undergoes synaptic changes in the course of aging and dementia. Previous studies attempting to assess the integrity of the PP in humans using diffusion tensor imaging (DTI) were limited by low resolution and the inability to identify PP fibers specifically. Here we present an application of DTI at ultrahigh submillimeter resolution that has allowed us to successfully identify diffusion signals unique to the PP and compare the intensity of these signals in a sample of young adults and older adults. We report direct evidence of age-related PP degradation in humans in vivo. We find no evidence of such loss in a control pathway, the alveus, suggesting that these findings are not evidence for a global decline. We also find no evidence for specific entorhinal gray matter atrophy. The extent of PP degradation correlated with performance on a word-list learning task sensitive to hippocampal deficits. We also show evidence for gray matter diffusion signals consistent with pyramidal dendrite orientation in the hippocampus and cerebral cortex. Ultrahigh-resolution microstructural DTI is a unique biomarker that can be used in combination with traditional structural and functional neuroimaging methods to enhance detection of Alzheimer disease in its earliest stages, test the effectiveness of new therapies, and monitor disease progression.

Resolution and contrast in magnetic resonance electrical impedance tomography (MREIT) and its application to cancer imaging.

It has been reported that the electrical impedance of malignancies could be 20–40 times lower than healthy tissues and benign formations. Therefore, in vivo impedance imaging of suspicious lesions may prove to be helpful in improving the sensitivity and specificity of detecting malignant tumors. Several systems have been developed to map the conductivity distribution inside a volume of tissue, however they suffer from poor spatial resolution because the measurements are taken only from surface electrodes. MRI based impedance imaging (MREIT) is a novel method, in which weak electrical currents are injected into the tissue and the resulting perturbations in the magnetic field are measured using MRI. This method has been shown to provide better resolution compared to previous techniques of impedance imaging because the measurements are taken from inside the object on a uniform grid. Thus, it has the potential to be a useful modality that may detect malignancies earlier. Several phantom imaging experiments were performed to investigate the spatial resolution and dynamic range of contrast of this technique. The method was also applied to a live rat bearing a R3230 AC tumor. Tumor location was identified by contrast enhanced imaging.

Multiple repetitions reveal functionally and anatomically distinct patterns of hippocampal activity during continuous recognition memory.

We used a continuous recognition procedure that included multiple presentations of test items, along with high‐resolution functional magnetic resonance imaging (fMRI), to investigate the relationship between item novelty and recognition‐related activity in the medial temporal lobe (MTL). In several regions of hippocampus and parahippocampal cortex, activity elicited by new items exceeded that for old items, whereas no MTL regions exhibited greater activity for old items. Critically, anatomically distinct regions of MTL were engaged by item novelty in two different ways, as evidenced by statistically dissociable profiles of activity. In bilateral medial hippocampus and left posterior parahippocampal cortex, activity followed a categorical profile in which it was greater for new than old items but did not differ further with additional presentations of old items. By contrast, effects in adjacent regions of right lateral hippocampus and left parahippocampal cortex were graded, whereby activity declined linearly with respect to each successive item presentation. These findings suggest that the relationship between hippocampal (and parahippocampal) activity and continuous psychological dimensions, such as item novelty, cannot be captured by a unitary function.

Development of an MR-compatible SPECT system (MRSPECT) for simultaneous data acquisition

In medical imaging, single-photon emission computed tomography (SPECT) can provide specific functional information while magnetic resonance imaging (MRI) can provide high spatial resolution anatomical information as well as complementary functional information. In this study, we developed a miniaturized dual-modality SPECT/MRI (MRSPECT) system and demonstrated the feasibility of simultaneous SPECT and MRI data acquisition, with the possibility of whole-body MRSPECT systems through suitable scaling of components. For our MRSPECT system, a cadmium-zinc-telluride (CZT) nuclear radiation detector was interfaced with a specialized radiofrequency (RF) coil and placed within a whole-body 4 T MRI system. Various phantom experiments characterized the interaction between the SPECT and MRI hardware components. The metallic components of the SPECT hardware altered the B(0) field and generated a non-uniform reduction in the signal-to-noise ratio (SNR) of the MR images. The presence of a magnetic field generated a position shift and resolution loss in the nuclear projection data. Various techniques were proposed to compensate for these adverse effects. Overall, our results demonstrate that accurate, simultaneous SPECT and MRI data acquisition is feasible, justifying the further development of MRSPECT for either small-animal imaging or whole-body human systems by using appropriate components.

Measurement of ion diffusion using magnetic resonance electrical impedance tomography

In magnetic resonance electrical impedance tomography (MREIT), currents are applied to an object, the resulting magnetic flux density measured using MRI and the conductivity distribution reconstructed using these MRI data. In this study, we assess the ability of MREIT to monitor changes in the conductivity distribution of an agarose gel phantom, using injected current pulses of 900 microA. The phantom initially contained a distinct region of high sodium chloride concentration which diffused into the background over time. MREIT data were collected over a 12 h span, and conductivity images were reconstructed using the iterative sensitivity matrix method with Tikhonov regularization. The results indicate that MREIT was able to monitor the changing conductivity and concentration distributions resulting from the diffusion of ions within the agarose gel phantom.

Cortical and subcortical changes in typically developing preadolescent children

There is evidence that abnormal cerebral development during childhood is a risk factor for various cognitive and psychiatric disorders. There is not, however, sufficient normative data available on large samples of typically developing children, especially within the narrow preadolescent age range. We analyzed high resolution MRI images from 126 normally developing children between ages 6 and 10 years. Age related differences in cortical thickness and in the volumes of major subcortical structures were assessed. Thinner cortices were observed in the occipital, parietal and somatosensory regions as well as in distinct regions of the temporal and frontal lobes with increasing age. Among the major subcortical structures analyzed in this study, only the thalamus showed increased volume with age after accounting for intracranial volume. Within the age range studied age-related cortical and subcortical differences were similar for boys and girls except for the right insula, where girls showed a slight increase in thickness with age. The findings reveal age-associated changes in brain anatomy, providing information about the trajectory of normal brain development during late childhood.

Contrast and spatial resolution in MREIT using low amplitude current

Magnetic resonance-electrical impedance tomography employs low amplitude currents injected or induced inside an object. The additional magnetic field due to these currents results in a phase in the MR images. In this study, a modified fast spin-echo sequence was used to measure this magnetic field, which is obtained by scaling the MR phase image. A finite element method with first order triangular elements was used for the solution of the forward problem. An iterated sensitivity matrix-based algorithm was developed for the inverse problem. The resulting ill-conditioned matrix equation was regularized using the Tikhonov method and solved using a conjugate gradient solver. The spatial and contrast resolution of the technique was tested using agarose gel phantoms. A circular phantom with 7 cm diameter and 1 cm thickness is used in the phantom experiments. The amplitude of the injected current was 1 mA. 3, 5 and 8 mm diameter insulators and high conductor objects are used for the spatial resolution study and an average full-width half-maximum value of 4.7 mm is achieved for the 3 mm insulator case. For the contrast analysis, the conductivity of a 15 mm object is varied between 44% and 500% with respect to the background and results are compared to the ideal reconstruction.