Plasma levels of TNF-α and MMP-9 in patients with silicosis.

OBJECTIVE: Silicosis is usually recognized at later stages of the disease, and early biomarkers for silicosis will be useful for timely diagnosis. We aimed at examining plasma levels of TNF-α and MMP-9, and correlation between these, in patients with different stages of silicosis in order to test suitability of these inflammatory factors as early biomarkers for silicosis. PATIENTS AND METHODS: TNF-α and MMP-9 were quantified by ELISA in plasma specimens from 30 healthy individuals (control group), 28 individuals exposed to silica dust but without clinical disease, and 30 patients with silicosis. RESULTS: Plasma levels of TNF-α and MMP-9 were increased in individuals exposed to silica dust (p < 0.05 vs. control individuals) and were further elevated in patients with silicosis (p < 0.05 vs. control individuals and individuals exposed to silica dust). There was a significant correlation between plasma levels of TNF-α and MMP-9 both in individuals exposed to silica dust (r = 0.696, p < 0.01) and patients with silicosis (r = 0.768, p < 0.01). CONCLUSIONS: Plasma levels of TNF-α and MMP-9 are increased prior to development of clinically recognized silicosis, suggesting that these biomarkers are involved in the onset and development of silicosis. Combined detection of TNF-α and MMP-9 may be useful for early diagnosis of silicosis.

Entanglement-based machine learning on a quantum computer.

Machine learning, a branch of artificial intelligence, learns from previous experience to optimize performance, which is ubiquitous in various fields such as computer sciences, financial analysis, robotics, and bioinformatics. A challenge is that machine learning with the rapidly growing "big data" could become intractable for classical computers. Recently, quantum machine learning algorithms [Lloyd, Mohseni, and Rebentrost, arXiv.1307.0411] were proposed which could offer an exponential speedup over classical algorithms. Here, we report the first experimental entanglement-based classification of two-, four-, and eight-dimensional vectors to different clusters using a small-scale photonic quantum computer, which are then used to implement supervised and unsupervised machine learning. The results demonstrate the working principle of using quantum computers to manipulate and classify high-dimensional vectors, the core mathematical routine in machine learning. The method can, in principle, be scaled to larger numbers of qubits, and may provide a new route to accelerate machine learning.

Dynamically controlled resonance fluorescence spectra from a doubly dressed single InGaAs quantum dot.

We report the first experimental demonstration of the interference-induced spectral line elimination predicted by Zhu and Scully [Phys. Rev. Lett. 76, 388 (1996)] and Ficek and Rudolph [Phys. Rev. A 60, R4245 (1999)]. We drive an exciton transition of a self-assembled quantum dot in order to realize a two-level system exposed to a bichromatic laser field and observe the nearly complete elimination of the resonance fluorescence spectral line at the driving laser frequency. This is caused by quantum interference between coupled transitions among the doubly dressed excitonic states, without population trapping. We also demonstrate a multiphoton ac Stark effect with shifted subharmonic resonances and dynamical modifications of resonance fluorescence spectra by using double dressing.

Selective homonuclear polarization transfer for spectroscopic imaging of GABA at 7T.

We develop and implement a selective homonuclear polarization transfer method for the detection of 3.0 ppm C-4 GABA resonance by spectroscopic imaging in the human brain at 7T. This single shot method is demonstrated with simulations and phantoms, which achieves comparable efficiency of detection to that of J-difference editing. The macromolecule resonance that commonly co-edits with GABA is suppressed at 7T through use of a narrow band preacquisition suppression pulse. This technique is implemented in humans with an eight channel transceiver array and high degree B(0) shimming to measure supplementary motor area and thalamic GABA in controls (n = 8) and epilepsy patients (n = 8 total). We find that the GABA/N-acetyl aspartate ratio in the thalamus of control volunteers, well controlled and poorly controlled epilepsy patients are 0.053 ± 0.012 (n = 8), 0.090 ± 0.012 (n = 2), and 0.038 ± 0.009 (n = 6), respectively.

Metabolic networks in epilepsy by MR spectroscopic imaging.

OBJECTIVE: The concept of an epileptic network has long been suggested from both animal and human studies of epilepsy. Based on the common observation that the MR spectroscopic imaging measure of NAA/Cr is sensitive to neuronal function and injury, we use this parameter to assess for the presence of a metabolic network in mesial temporal lobe epilepsy (MTLE) patients. MATERIALS AND METHODS: A multivariate factor analysis is performed with controls and MTLE patients, using NAA/Cr measures from 12 loci: the bilateral hippocampi, thalami, basal ganglia, and insula. The factor analysis determines which and to what extent these loci are metabolically covarying. RESULTS: We extract two independent factors that explain the data's variability in control and MTLE patients. In controls, these factors characterize a 'thalamic' and 'dominant subcortical' function. The MTLE patients also exhibit a 'thalamic' factor, in addition to a second factor involving the ipsilateral insula and bilateral basal ganglia. CONCLUSIONS: These data suggest that MTLE patients demonstrate a metabolic network that involves the thalami, also seen in controls. The MTLE patients also display a second set of metabolically covarying regions that may be a manifestation of the epileptic network that characterizes limbic seizure propagation.

J-refocused coherence transfer spectroscopic imaging at 7 T in human brain.

Short echo spectroscopy is commonly used to minimize signal modulation due to J-evolution of the cerebral amino acids. However, short echo acquisitions suffer from high sensitivity to macromolecules which make accurate baseline determination difficult. In this report, we describe implementation at 7 T of a double echo J-refocused coherence transfer sequence at echo time (TE) of 34 msec to minimize J-modulation of amino acids while also decreasing interfering macromolecule signals. Simulation of the pulse sequence at 7 T shows excellent resolution of glutamate, glutamine, and N-acetyl aspartate. B(1) sufficiency at 7 T for the double echo acquisition is achieved using a transceiver array with radiofrequency (RF) shimming. Using an alternate RF distribution to minimize receiver phase cancellation in the transceiver, accurate phase determination for the coherence transfer is achieved with rapid single scan calibration. This method is demonstrated in spectroscopic imaging mode with n = 5 healthy volunteers resulting in metabolite values consistent with literature and in a patient with epilepsy.

Single stage transmission type broadband solar concentrator.

In this paper, a single stage solar cell concentrator is designed and discussed. The proposed concentrator consists of refraction prisms and total internal reflection prisms in the inner and outer areas, respectively. In order to compensate for dispersion, all odd zones gather the light onto the -D position, while all even zones gather the light onto the + D position. Finally, the hybrid concentrator achieves optical efficiency of 89.8% for normally incident light without an antireflection coating. An acceptance angle of +/- 0.78 degree at 1 dB loss is achieved without using additional secondary optics. In addition, the fabrication tolerance is also analyzed.

Hippocampal correlates of pain in healthy elderly adults: a pilot study.

BACKGROUND: Few neuroimaging investigations of pain in elderly adults have focused on the hippocampus, a brain structure involved in nociceptive processing that is also subject to involution associated with dementing disorders. The goal of this pilot study was to examine MRI- and magnetic resonance spectroscopy (MRS)-derived hippocampal correlates of pain in older adults. METHODS: A subset of 20 nondemented older adults was drawn from the Einstein Aging Study, a community-based sample from the Bronx, NY. Pain was measured on 3 time scales: 1) acute pain right now (pain severity); 2) pain over the past 4 weeks (Short Form-36 Bodily Pain); 3) chronic pain over the past 3 months (Total Pain Index). Hippocampal data included volume data normalized to midsagittal area and N-acetylaspartate to creatine ratios (NAA/Cr). RESULTS: Smaller hippocampal volume was associated with higher ratings on the Short Form-36 Bodily Pain (r(s) = 0.52, p = 0.02) and a nonsignificant trend was noted for higher ratings of acute pain severity (r(s) = -0.44, p = 0.06). Lower levels of hippocampal NAA/Cr were associated with higher acute pain severity (r(s) = -0.45, p = 0.05). Individuals with chronic pain had a nonsignificant trend for smaller hippocampal volumes (t = 2.00, p = 0.06) and lower levels of hippocampal NAA/Cr (t = 1.71, p = 0.10). CONCLUSIONS: Older adults who report more severe acute or chronic pain have smaller hippocampal volumes and lower levels of hippocampal N-acetylaspartate/creatine, a marker of neuronal integrity. Future studies should consider the role of the hippocampus and other brain structures in the development and experience of pain in healthy elderly and individuals with Alzheimer disease.

Intracranial EEG power and metabolism in human epilepsy.

EEG power and high frequency activity in the seizure onset zone has been increasingly considered for its relationship with seizures in animal and human studies of epilepsy. We examine the relationship between quantitative EEG measures and metabolic imaging in epilepsy patients undergoing intracranial EEG (icEEG) analysis for seizure localization. Patients with mesial temporal lobe epilepsy (MTLE) and neocortical epilepsy (NE) were studied. Metabolic imaging was performed with MR spectroscopic imaging using N-acetyl aspartate (NAA) and creatine (Cr). All data were acquired from the mesial temporal lobe such that a direct comparison of the same anatomical regions between the two groups could be performed. While no difference was seen in the total power recorded from the mesial temporal lobe, the MTLE group had significantly greater power in the high frequency bands. There was a significant positive exponential relationship between total icEEG power with NAA/Cr in MTLE, R=+0.84 and p<0.001, which was not seen in NE. There was also a significant negative relationship between fractional gamma power with NAA/Cr in MTLE, R=-0.66 and p<0.02, also not seen in NE. These data argue that within the seizure onset zone, the tight correlation between total power and NAA/Cr suggests that total electrical output is powered by available mitochondrial function. These data are also consistent with the hypothesis that high frequency activity is an abnormal manifestation of tissue injury.

Short echo spectroscopic imaging of the human brain at 7T using transceiver arrays.

Recent advances in magnet technology have enabled the construction of ultrahigh-field magnets (7T and higher) that can accommodate the human head and body. Despite the intrinsic advantages of performing spectroscopic imaging at 7T, increased signal-to-noise ratio (SNR), and spectral resolution, few studies have been reported to date. This limitation is largely due to increased power deposition and B(1) inhomogeneity. To overcome these limitations, we used an 8-channel transceiver array with a short TE (15 ms) spectroscopic imaging sequence. Utilizing phase and amplitude mapping and optimization schemes, the 8-element transceiver array provided both improved efficiency (17% less power for equivalent peak B(1)) and homogeneity (SD(B(1)) = +/-10% versus +/-22%) in comparison to a transverse electromagnetic (TEM) volume coil. To minimize the echo time to measure J-modulating compounds such as glutamate, we developed a short TE sequence utilizing a single-slice selective excitation pulse followed by a broadband semiselective refocusing pulse. Extracerebral lipid resonances were suppressed with an inversion recovery pulse and delay. The short TE sequence enabled visualization of a variety of resonances, including glutamate, in both a control subject and a patient with a Grade II oligodendroglioma.

Supratentorial Brain AVM Embolization with Onyx-18 and Post-Embolization Management. A Single-Center Experience.

SUMMARY: Onyx is increasingly used in endovascular therapy of intracranial arteriovenous malformations (AVMs). However, the embolic effect and post-embolization management are still under discussion. We report our experience in the treatment of supratentorial brain arteriovenous malformations (SBAVMs) with Onyx and discuss post-embolic management. From June 2006 to July 2008, 20 patients with SBAVM were embolized with Onyx. There were 14 men and six women ranging from 14 to 64 years of age (mean 38.3 years). Initial symptoms included spontaneous hemorrhage (n=12), headaches (n=4), seizure (n=3) and incidentally disclosed after head trauma (n=1). After the endovascular procedure, all had subsequent treatment (follow-up angiogram, stereotactic radiosurgery or microsurgery) according to the obliteration degree. At angiography, seven patients (35%, 7/20) were completely obliterated (over 95% closure) after embolization while one suffered a small subarachnoid hemorrhage without permanent clinical sequelae. Four patients (20%, 4/20) were subtotally obliterated (over 80% closure), one patient who suffered severe cerebral edema after embolization underwent decompressive craniectomy, two patients had additional radiosurgery and one patient had follow-up angiogram. Nine patients (45%, 9/20) were partially obliterated (20-80% closure), five patients had additional surgery, two patients had additional radiosurgery and two patients had follow-up angiogram (one patient had intraventricular hemorrhage three months after embolization). Of all 20 AVMs, an average of 2.2 ml Onyx was used per patient and average volume reduction was 80% (range, 30%-99%). Onyx is suitable for embolization of SBAVMs because of its diffuse controllable properties. We suggest clinical follow-up after complete obliteration, additional radiosurgery or angiographic follow-up after subtotal obliteration and additional surgery after partially obliteration. More cases with long-term follow-up are needed to evaluate the long-term prognosis of our post-embolization management.

Hippocampal extracellular GABA correlates with metabolism in human epilepsy.

As the major inhibitory neurotransmitter in human brain, GABA is an important modulator of hyperexcitability in epilepsy patients. Given the high energetic cost of neurotransmission and synaptic activity, GABA concentrations may be hypothesized to correlate with metabolic function. We studied human epilepsy patients undergoing intracranial EEG monitoring for seizure localization to examine microdialysis measures of extracellular GABA (ecGABA), pre-operative MR spectroscopic measures of neuronal mitochondrial function (NAA/Cr), and wherever possible, neuropathology and hippocampal volumetry. Two groups undergoing intracranial monitoring for seizure localization were studied: surgically treated hippocampal epilepsy (MTLE) and neocortical (non-hippocampal seizure onset) epilepsy. All data are hippocampal and thus these groups allow comparisons between the epileptogenic and non-epileptogenic regions. ecGABA was measured using in vivo microdialysis performed during intracranial monitoring. Pre-operative in vivo MR spectroscopic imaging was performed to measure the ratio of N-acetyl aspartate (NAA) to creatine. Standard methods for neuropathology and hippocampal volumetry were used. In the neocortical group, increased ecGABA correlated with greater NAA/Cr (R = +0.70, p < 0.015, n = 12) while in the MTLE group, increased ecGABA linked with decreased NAA/Cr (R = -0.94, p < 0.001, n = 8). In MTLE, ecGABA (increased) and NAA/Cr (decreased) correlated with increased glial cell numbers (R = +0.71, p < 0.01, n = 12, R = -0.76 p < 0.03 respectively). No relationship was seen between ecGABA and hippocampal volumes in either group. In epilepsy, ecGABA increases occur across a range of metabolic function. Outside the seizure focus, ecGABA and NAA/Cr increase together; in contrast, within the seizure focus, ecGABA increases with declining mitochondrial function.

Hippocampal neurochemistry, neuromorphometry, and verbal memory in nondemented older adults.

BACKGROUND: Characterization of the behavioral correlates of neuromorphometry and neurochemistry in older adults has important implications for an improved understanding of the aging process. The objective of this study was to test the hypothesis that a measure of hippocampal neuronal metabolism was associated with verbal memory in nondemented older adults after controlling for hippocampal volume. METHODS: 4-T MRI, proton magnetic resonance spectroscopy ((1)H MRS), and neuropsychological assessment were conducted in 48 older adults (23 women; mean age 81 years). Average hippocampal N-acetyl aspartate/creatine ratios (NAA/Cr) and hippocampal volumes were obtained. Neuropsychological evaluation included tests of verbal memory (Buschke and Grober Free and Cued Selective Reminding Test-Immediate Recall [FCSRT-IR], Wechsler Memory Scale-Revised Logical Memory subtest) and attention and executive function (Trail Making Test Parts A and B). RESULTS: Linear regression analysis indicated that after adjusting for age, hippocampal NAA/Cr was a significant predictor of FCSRT-IR performance (beta = 0.38, p = 0.01, R (2) = 0.21). Hippocampal volume was also a significant predictor of FCSRT-IR performance after adjusting for age and midsagittal area (beta = 0.47, p = 0.01, R (2) = 0.24). In a combined model, hippocampal NAA/Cr (beta = 0.33, p = 0.03) and volume (beta = 0.35, p = 0.03) were independent predictors of FCSRT-IR performance, accounting for 30% of the variance in memory. CONCLUSIONS: These findings indicate that nondemented older adults with smaller hippocampal volumes and lower levels of hippocampal N-acetyl aspartate/creatine ratio metabolites perform more poorly on a test of verbal memory. The integrity of both the structure and metabolism of the hippocampus may underlie verbal memory function in nondemented elderly.

A subcortical network of dysfunction in TLE measured by magnetic resonance spectroscopy.

OBJECTIVE: The goal of this work was to evaluate the relationship between neuronal injury/loss in the hippocampus, thalamus, and putamen in temporal lobe epilepsy (TLE) patients using (1)H magnetic resonance spectroscopic imaging. METHODS: (1)H spectroscopic images from the hippocampus and thalamus of controls and patients with TLE were acquired at 4 T. The spectroscopic imaging data were reconstructed using an automated voxel-shifting method based on anatomic landmarks providing four, six, and three loci for the hippocampus, thalamus, and putamen, respectively. For correlation analysis, the hippocampal and striatal loci were averaged to provide single estimates of the entire structure, whereas the thalamus was divided into two regions, an anterior and posterior measure, using the average of three loci each. RESULTS: The ratio of N-acetyl aspartate to creatine (NAA/Cr), a measure of neuronal injury/loss, was significantly reduced in both the ipsilateral and contralateral hippocampi and thalami. NAA/Cr in the ipsilateral hippocampus was significantly correlated with the ipsilateral and contralateral anterior and posterior thalami, putamen, and contralateral hippocampus. In control subjects, the hippocampi were only correlated with each other. CONCLUSIONS: The data demonstrate that there is significant neuronal injury/loss in both the ipsilateral and contralateral thalami in temporal lobe epilepsy patients, with greater impairment in the anterior portions of the ipsilateral thalamus. The degree of injury/loss in the ipsilateral and contralateral thalamus and putamen is directly correlated with that of the ipsilateral hippocampus. This is consistent with the hypothesis that the impairment and damage associated with recurrent seizures as measured by N-acetyl aspartate originating in the hippocampus results in injury and impairment in other subcortical structures.

Cerebral energetic effects of creatine supplementation in humans.

There has been considerable interest in the use of creatine (Cr) supplementation to treat neurological disorders. However, in contrast to muscle physiology, there are relatively few studies of creatine supplementation in the brain. In this report, we use high-field MR (31)P and (1)H spectroscopic imaging of human brain with a 7-day protocol of oral Cr supplementation to examine its effects on cerebral energetics (phosphocreatine, PCr; ATP) and mitochondrial metabolism (N-acetyl aspartate, NAA; and Cr). We find an increased ratio of PCr/ATP (day 0, 0.80 +/- 0.10; day 7, 0.85 +/- 09), with this change largely due to decreased ATP, from 2.7 +/- 0.3 mM to 2.5 +/- 0.3 mM. The ratio of NAA/Cr also decreased (day 0, 1.32 +/- 0.17; day 7 1.18 +/- 0.13), primarily from increased Cr (9.6 +/- 1.9 to 10.1 +/- 2.0 mM). The Cr-induced changes significantly correlated with the basal state, with the fractional increase in PCr/ATP negatively correlating with the basal PCr/ATP value (R = -0.74, P < 0.001). As NAA is a measure of mitochondrial function, there was also a significant negative correlation between basal NAA concentrations with the fractional change in PCr and ATP. Thus healthy human brain energetics is malleable and shifts with 7 days of Cr supplementation, with the regions of initially low PCr showing the largest increments in PCr. Overall, Cr supplementation appears to improve high-energy phosphate turnover in healthy brain and can result in either a decrease or an increase in high-energy phosphate concentrations.

Quantitative glutamate spectroscopic imaging of the human hippocampus.

We have evaluated a three-dimensional localized spectroscopic imaging sequence that uses two pairs of adiabatic full-passage pulses, which optimizes the detection of glutamate resonances at moderate echo times. This sequence provides excellent volume localization while simultaneously reducing J-modulation losses of glutamate. We have simulated the performance of this sequence for glutamate and used it to quantitatively measure glutamate in the human hippocampus using a linear components model. Using tissue segmentation and regression analysis, we measured a glutamate concentration of 8.8 +/- 2.1 mM in hippocampal and temporal gray matter and 3.7 +/- 1.1 mM in temporal white matter (95% CI). We have used this approach in a small group of patients (n = 5) with unilateral hippocampal epilepsy.

Quantum nonlocality obtained from local states by entanglement purification.

We have applied an entanglement purification protocol to produce a single entangled pair of photons capable of violating a Clauser-Horne-Shimony-Holt Bell inequality from two pairs that individually could not. The initial poorly entangled photons were created by a controllable decoherence that introduced complex errors. All of the states were reconstructed using quantum state tomography which allowed for a quantitative description of the improvement of the state after purification.

Regional energetic dysfunction in hippocampal epilepsy.

OBJECTIVES: There is increasing evidence for a dysfunctional metabolic network in human mesial temporal lobe epilepsy (MTLE). To further describe this, we evaluated the bioenergetic status in unilateral MTLE inter-regionally and in relation to neuropathology. MATERIALS AND METHODS: We used whole brain high field (4 T) 31P MR spectroscopic imaging to determine in vivo PCr and ATP, studying n=22 patients (all candidates for hippocampal resection) and n=14 control volunteers. The degree of bioenergetic impairment was assessed by calculating the ratio of PCr to ATP. RESULTS: Compared to controls, patients demonstrated significant decreases in PCr/ATP from the ipsilateral amygdala and pes (0.84 +/- 0.14, 0.87 +/- 0.10, respectively, patients vs 0.97 +/- 0.15, 0.98 +/- 0.16, controls). In patients, the ipsilateral thalamic energetics positively correlated with contralateral hippocampal energetics. In addition, the ipsilateral thalamic and striatal energetics negatively correlated with hippocampal total glial counts. CONCLUSIONS: These data are consistent with a view that in MTLE, the bilateral hippocampi, ipsilateral thalamus and striatum are linked in their energetic depression, possibly reflecting the propagation of seizures throughout the brain.

Metabolic differences between multiple sclerosis subtypes measured by quantitative MR spectroscopy.

We used quantitative magnetic resonance (MR) spectroscopic imaging with T1-based image segmentation to evaluate the subtypes of multiple sclerosis (MS) (eight patients each group of relapsing-remitting [RR], secondary progressive [SP] and primary progressive [PP]). There was no significant difference in age between the PP group with the RP, SP or control group. We found that the metabolite ratio of choline/NA from the periventricular white matter region was not significantly different between the RR and SP groups. Using an ANOVA, the ratios of periventricular choline/NA or creatine/NA of these combined groups were significantly higher than the PP and control groups. Quantification of these data suggest that the major cause of the elevation of these parameters is due to an increase in choline and creatine in the RR group while NA is decreased in the SP group. Thus, early PP disease appears to be relatively intact with respect to neuronal loss.