Locus Coeruleus magnetic resonance imaging: a comparison between native-space and template-space approach.

Locus Coeruleus (LC) is the main noradrenergic nucleus of the brain, which is involved in many physiological functions including cognition; its impairment may be crucial in the neurobiology of a variety of brain diseases. Locus Coeruleus-Magnetic Resonance Imaging (LC-MRI) allows to identify in vivo LC in humans. Thus, a variety of research teams have been using LC-MRI to estimate LC integrity in normal aging and in patients affected by neurodegenerative disorders, where LC integrity my work as a biomarker. A number of variations between LC-MRI studies exist, concerning post-acquisition analysis and whether this had been performed within MRI native space or in ad hoc-built MRI template space. Moreover, the reproducibility and reliability of this tool is still to be explored. Therefore, in the present study, we analyzed a group of neurologically healthy, cognitively intact elderly subjects, using both a native space- and a template space-based LC-MRI analysis. We found a good inter-method agreement, particularly considering the LC Contrast Ratio. The template space-based approach provided a higher spatial resolution, lower operator-dependency, and allowed the analysis of LC topography. Our ad hoc-developed LC template showed LC morphological data that were in line with templates published very recently. Remarkably, present data significantly overlapped with a recently published LC "metaMask", that had been obtained by averaging the results of a variety of previous LC-MRI studies. Thus, such a template space-based approach may pave the way to a standardized LC-MRI analysis and to be used in future clinic-anatomical correlations.

Rapid bedside rejuvenation of red blood cell with an autologous cell salvage device.

BACKGROUND AND OBJECTIVES: During storage, red blood cells (RBCs) undergo physicochemical changes which affect the quality, function, and in vivo survival of transfused packed RBCs (pRBC). Changes include decreased 2,3-diphosphoglycerate (2,3-DPG) levels, decreased ATP, changes in mechanical properties and oxidative injury. RBC rejuvenation is a method used to increase levels of 2,3-DPG and ATP in pRBCs. This process requires incubating the pRBCs with a rejuvenation solution and subsequent washing. Standard blood bank protocols using the COBE 2991 Cell Processor require several hours of preparation. The objective of this study was to verify if a bedside protocol for rejuvenating pRBC and washing with the Sorin Xtra autologous cell salvage system could be used. MATERIALS AND METHODS: Outdated pRBC units were obtained and rejuvenated in a model operating suite using a dry air incubator for 1 h at 37°C. Six units of pRBCs were pre-diluted with saline (1000 ml) and six units were not pre-diluted with saline. All units were washed with normal saline (1000 ml) using an apheresis-design cell salvage device in manual mode and wash volume set to 3000 ml. Samples were collected and analyzed for standard RBC quality parameters at baseline and post-wash. RESULTS: Total pRBC wash efficiency was 94% ± 12% at a final hematocrit of 67.7 ± 5.9% while maintaining post-wash hemolysis 0.24 ± 0.12 %. Pre-dilution prior to washing did not confer statistically significant differences in final RBC quality parameters with the notable exceptions of calculated hemolysis and supernatant potassium levels (P < 0.05). The washing process can be completed within 10 min. The post-wash RBC parameters are appropriate for immediate transfusion to patients.

A novel easy-to-use phantom for the determination of MTF in SPECT scanners.

PURPOSE: To evaluate modulation transfer function (MTF) in single photon emission computed tomography (SPECT) systems using the line spread function (LSF) method and a novel flood source which can be easily fabricated with materials accessible in hospital facilities. METHODS: A Tc-99m-based flood source (E(γ) = 140 keV) consisting of a radiopharmaceutical bound to the grains of a radiographic film was prepared in laboratory. Various films and radiopharmaceuticals were examined, in order to obtain a thin homogenous and reproducible flood source. The source showing best uniformity and reproducibility was placed between two PMMA blocks and images were obtained by using the brain tomographic acquisition protocol (brain) and the myocardial perfusion tomographic acquisition protocol (heart). MTF was evaluated by determining the LSF for various reconstruction methods and filters. MTF calculation was obtained by the utilization of a custom made software in which a method similar to the one proposed by Boone [Med. Phys. 28, 356-360 (2001)] was implemented. All imaging experiments were performed in a Siemens e-Cam γ-camera. Furthermore, MTF was assessed through the point spread function (PSF) following conventional methods. RESULTS: The optimum homogeneity was obtained by immersing an Agfa MammoRay HDR Medical x-ray film in a solution of dithiothreitol (DTT, 10(-3) M)/Tc-99m(III)-DMSA (DMSA: trivalent technetium-99m-dimercapto-succinic acid, 40 mCi/40 ml) for 30 min in the dark. These films exhibited better uniformity (CV < 1.9%). Higher MTF values were obtained for the brain scan protocol with iterative 3D with eight iterations reconstruction method. MTF of the brain protocol was in all cases better than the heart protocol. MTFs derived from LSF were more precise compared with those obtained from PSF since their reproducibility was better in all cases, providing a mean standard deviation of 0.0065, in contrary to the PSF method which gave 0.0348. CONCLUSIONS: The method presented here is novel and easy to implement, requiring materials commonly found in clinical practice. Furthermore, this technique which is based on the LSF method reduces measurement noise levels due to the larger amount of data averaging than in the conventional PSF method. Furthermore, MTF can be assessed easily, in three dimensions (3D), by placing the flood source either in sagittal or coronal direction.

Noise correlations and SNR in phased-array MRS.

The acquisition of magnetic resonance spectroscopy (MRS) signals by multiple receiver coils can improve the signal-to-noise ratio (SNR) or alternatively can reduce the scan time maintaining a reliable SNR. However, using phased array coils in MRS studies requires efficient data processing and data combination techniques in order to exploit the sensitivity improvement of the phased array coil acquisition method. This paper describes a novel method for the combination of MRS signals acquired by phased array coils, even in presence of correlated noise between the acquisition channels. In fact, although it has been shown that electric and magnetic coupling mechanisms produce correlated noise in the coils, previous algorithms developed for MRS data combination have ignored this effect. The proposed approach takes advantage of a noise decorrelation stage to maximize the SNR of the combined spectra. In particular Principal Component Analysis (PCA) was exploited to project the acquired spectra in a subspace where the noise vectors are orthogonal. In this subspace the SNR weighting method will provide the optimal overall SNR. Performance evaluation of the proposed method is carried out on simulated (1)H-MRS signals and experimental results are obtained on phantom (1)H-MR spectra using a commercially available 8-element phased array coil. Noise correlations between elements were generally low due to the optimal coil design, leading to a fair SNR gain (about 0.5%) in the center of the field of view (FOV). A greater SNR improvement was found in the peripheral FOV regions.

A New Point Mutation in the PMP22 Gene in a Family Suffering From Atypical HNPP.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant inherited disorder commonly presenting with acute-onset, non-painful focal sensory and motor mono neuropathy. In 80% of cases, the genetic defect is a 1.5 Mb deletion on chromosome 17p11.2, including PMP22. Only few cases of partial deletion and point mutations in PMP22 are involved in HNPP. We investigated a 62-years-old man with lower limb plexopathy first considered as Garland's syndrome. A month later, his 29 years old son also consulted for paresthesia on the peroneal nerve.Targeted sequencing of the PMP22 gene identified a c.370delT (p.Trp124Glyfs*31) in both affected patients.We report a new PMP22 point mutation associated with an atypical clinical phenotype of HNPP, a painful plexopathy of the lower limb worsenen by diabetes and a mere paresthesia, but a typical ENMG. This study illustrates the large spectrum of the disease, and emphasizes the importance of a complete ENMG and family history.

Modification of plant lipid synthesis.

Genetic engineering of new storage oils and fats has produced oil crop plants with fatty acid compositions unattainable by plant breeding alone. The combination of classical breeding methods with molecular techniques provides new ways for designing oils for food and nonfood uses. Alterations in the position and number of double bonds, variation in fatty acid chain length, and the introduction of desired functional groups have already been achieved in model systems. Short-term prospects include crops such as rapeseed or soybean engineered to have greater than 70 to 80 percent medium-chain fatty acids by content, greater than 90 percent oleic acid, and high erucic acid content, and engineered to form ricinoleic acid in seed storage tissues.

Objective selection of EEG late potentials through residual dependence estimation of independent components.

This paper presents a novel method to objectively select electroencephalographic (EEG) cortical sources estimated by independent component analysis (ICA) in event-related potential (ERP) studies. A proximity measure based on mutual information is employed to estimate residual dependences of the components that are then hierarchically clustered based on these residual dependences. Next, the properties of each group of components are evaluated at each level of the hierarchical tree by two indices that aim to assess both cluster tightness and physiological reliability through a template matching process. These two indices are combined in three different approaches to bring to light the hierarchical structure of the cluster organizations. Our method is tested on a set of experiments with the purpose of enhancing late positive ERPs elicited by emotional picture stimuli. Results suggest that the best way to look for physiologically plausible late positive potential (LPP) sources is to explore in depth the tightness of those clusters that, taken together, best resemble the template. According to our results, after brain sources clustering, LPPs are always identified more accurately than from ensemble-averaged raw data. Since the late components of an ERP involve the same associative areas, regardless of the modality of stimulation or specific tasks administered, the proposed method can be simply adapted to other ERP studies, and extended from psychophysiological studies to pathological or sport training evaluation support.

Independent component analysis applied to the removal of motion artifacts from electrocardiographic signals.

Electrocardiographic (ECG) signals are affected by several kinds of artifacts that may hide vital signs of interest. In this study we apply independent component analysis (ICA) to isolate motion artifacts. Standard or instantaneous ICA, which is currently the most addressed ICA model within the context of artifact removal, is compared to two other ICA techniques. The first technique is a frequency domain approach to convolutive mixture separation. The second is based on temporally constrained ICA, which enables the estimation of only one component close to a particular reference signal. Performance indexes evaluate ECG complex enhancement and relevant heart rate errors. Our results show that both convolutive and constrained ICA implementations perform better than standard ICA, thus opening up a new field of application for these two methods. Moreover, statistical analysis reveals that constrained ICA and convolutive ICA do not significantly differ concerning heart rate estimation, even though the latter overcomes the former in ECG morphology recovery.

Characterization of breast calcification types using dual energy x-ray method.

Calcifications are products of mineralization whose presence is usually associated with pathological conditions. The minerals mostly seen in several diseases are calcium oxalate (CaC2O4), calcium carbonate (CaCO3) and hydroxyapatite (HAp). Up to date, there is no in vivo method that could discriminate between minerals. To this aim, a dual energy x-ray method was developed in the present study. An analytical model was implemented for the determination of the Calcium/Phosphorus mass ratio ([Formula: see text]). The simulation was carried out using monoenergetic and polyenergetic x-rays and various calcification thicknesses (100-1000 [Formula: see text]) and types (CaC2O4, CaCO3, HAp). The experimental evaluation of the method was performed using the optimized irradiation conditions obtained from the simulation study. X-ray tubes, combined with energy dispersive and energy integrating (imaging) detectors, were used for the determination of the [Formula: see text] in phantoms of different mineral types and thicknesses. Based on the results of the experimental procedure, statistical significant difference was observed between the different types of minerals when calcification thicknesses were 300 [Formula: see text] or higher.

Actively controlled release of Dexamethasone from neural microelectrodes in a chronic in vivo study.

Stable interconnection to neurons in vivo over long time-periods is critical for the success of future advanced neuroelectronic applications. The inevitable foreign body reaction towards implanted materials challenges the stability and an active intervention strategy would be desirable to treat inflammation locally. Here, we investigate whether controlled release of the anti-inflammatory drug Dexamethasone from flexible neural microelectrodes in the rat hippocampus has an impact on probe-tissue integration over 12 weeks of implantation. The drug was stored in a conducting polymer coating (PEDOT/Dex), selectively deposited on the electrode sites of neural probes, and released on weekly basis by applying a cyclic voltammetry signal in three electrode configuration in fully awake animals. Dex-functionalized probes provided stable recordings and impedance characteristics over the entire chronic study. Histological evaluation after 12 weeks of implantation revealed an overall low degree of inflammation around all flexible probes whereas electrodes exposed to active drug release protocols did have neurons closer to the electrode sites compared to controls. The combination of flexible probe technology with anti-inflammatory coatings accordingly offers a promising approach for enabling long-term stable neural interfaces.

Aberrant p53 expression predicts clinical resistance to cisplatin-based chemotherapy in locally advanced non-small cell lung cancer.

The development of cisplatin-based induction chemotherapy followed by surgical resection or radiation has improved the poor prognosis of stage III non-small cell lung cancer (NSCLC). In vitro studies indicate that p53 can modulate cisplatin-induced cytotoxicity, but the molecular genetic features determining response or resistance to cisplatin in vivo must be defined. For this reason, tumor specimens from 52 patients with stage IIIA NSCLC entered in a prospective clinical trial of cisplatin-based induction chemotherapy followed by surgical resection were examined for p53 expression by immunohistochemical staining before and after induction chemotherapy. p53 expression was correlated with clinical and pathological response using Fisher's exact test. No correlation was established between p53 expression and clinical response because 47 of the 52 patients studied had a major response. However, a significant association was observed between aberrant p53 expression and resistance to chemotherapy as assessed by pathological response. Only 3 of the 20 patients whose tumors exhibited a high level (+ + to + + + +) of p53 staining experienced a major (+ + + to + + + +) pathological response to chemotherapy. Only 7 of 52 cases examined before and after chemotherapy treatment exhibited a change in the level of p53 expression after cisplatin-based chemotherapy. These results indicate that cisplatin alters p53 expression infrequently and suggest a direct link between aberrant p53 expression and resistance to cisplatin-based chemotherapy in NSCLC.

Polynomial dual energy inverse functions for bone Calcium/Phosphorus ratio determination and experimental evaluation.

An X-ray dual energy (XRDE) method was examined, using polynomial nonlinear approximation of inverse functions for the determination of the bone Calcium-to-Phosphorus (Ca/P) mass ratio. Inverse fitting functions with the least-squares estimation were used, to determine calcium and phosphate thicknesses. The method was verified by measuring test bone phantoms with a dedicated dual energy system and compared with previously published dual energy data. The accuracy in the determination of the calcium and phosphate thicknesses improved with the polynomial nonlinear inverse function method, introduced in this work, (ranged from 1.4% to 6.2%), compared to the corresponding linear inverse function method (ranged from 1.4% to 19.5%).

The combined neurosurgical-thoracic management of superior sulcus tumors.

Thirty patients with superior sulcus carcinoma were prospectively evaluated over an 18-month period. All patients underwent complete neuroradiological evaluation by computed tomography (CT) and myelography. Prior to operation, brachial plexopathy was noted in 20 patients (67%), and invasion of the spine in eight (27%). Using a team approach, gross total resection of tumor was achieved in 17 of 26 patients (65%) undergoing thoracotomy. There was no operative mortality. The use of a team approach allows extended surgical resection, especially when the spine is involved. In patients presenting with brachial plexopathy or cord compression, de novo surgery before radiation may provide better long-term palliation and pain relief.

The results of chemotherapy for extragonadal germ-cell tumors in the cisplatin era: the Memorial Sloan-Kettering Cancer Center experience (1975 to 1982).

Thirty-eight patients with extragonadal germ-cell tumors treated at Memorial Sloan-Kettering Cancer Center (New York) between 1975 and 1982 received high-dose cisplatin-based chemotherapy. Complete response was achieved in 89% of patients with pure seminoma and all complete responders are alive without evidence of disease (median follow-up time, 29+ months). Complete response was achieved in only 41% (12 of 29) of patients with extragonadal nonseminomatous germ-cell tumors; only four patients are alive and free of disease (median survival time, 18 months). Although patients with extragonadal seminoma respond well with current cisplatin-based chemotherapy, minimal improvement in CR rates has been achieved in patients with extragonadal nonseminomatous tumors. Patients with extragonadal nonseminomatous germ-cell tumors have a relatively poor prognosis when compared to patients with primary testicular tumors and investigational trials of innovative therapy should be considered.

Pathologic complete response in advanced non-small-cell lung cancer following preoperative chemotherapy: implications for the design of future non-small-cell lung cancer combined modality trials.

PURPOSE: This report determines the incidence of pathologic complete response in patients with locally advanced non-small-cell lung cancer (NSCLC) treated with mitomycin, vinca alkaloid, and high-dose cisplatin (MVP) chemotherapy, and estimates the effect of MVP on survival. PATIENTS AND METHODS: We have identified and reviewed the course of 21 patients with advanced NSCLC who achieved a pathologic complete response following a median of three preoperative MVP combination chemotherapy courses including vinblastine or vindesine, cisplatin (120 mg/m2), and mitomycin (n = 19). RESULTS: All patients had a major objective response following preoperative chemotherapy and nine (43%) had a clinical complete response. Nine patients with pathologic complete responses were among 73 entered on a preoperative chemotherapy program, yielding an incidence estimate of 12% (95% confidence interval, 6% to 22%). The median survival duration for all 21 patients has not been reached. The median follow-up duration is now 68 months (range, 17 to 109). Survival estimates are 90% at 1 year, 62% at 3 years, and 54% at 5 years. Nine patients have relapsed with initial sites of recurrence as follows: brain (n = 5), other systemic sites (n = 3), and locoregional (n = 1). One patient died in the postoperative period. Eleven patients remain disease-free and all have excellent functional status. CONCLUSION: We have observed pathologic complete responses in approximately 12% of advanced NSCLC patients treated with preoperative MVP chemotherapy. These pathologically determined responses were seen only in patients with major objective responses clinically. Pathologic complete response predicts excellent survival and functional level and should be considered a major end point in the evaluation of preoperative chemotherapy programs.

VAB-6: an effective chemotherapy regimen for patients with germ-cell tumors.

One hundred sixty-six patients with germ-cell tumors (GCT) of the testis, retroperitoneum, and mediastinum were treated with cyclophosphamide, vinblastine, bleomycin, dactinomycin, and cisplatin (VAB-6), with and without maintenance chemotherapy. The overall complete response (CR) rate was 78%, 67% to chemotherapy alone, and 11% after chemotherapy and resection of viable residual cancer. The CR rate in all patients with seminoma was uniformly high, while the CR rate of patients with testicular nonseminomatous germ-cell tumors (79%) was superior to that of similar tumors of extragonadal origin (60%). The overall relapse rate was 12%, and was greater in tumors of extragonadal origin (21%) than in those of testicular origin (11%). Three relapses occurred after 2 years. Maintenance chemotherapy did not prolong either relapse-free or total survival. Toxicity was tolerable, and there were no treatment deaths. No Raynaud's phenomena have occurred, with a minimum duration since start of therapy of 36 months. VAB-6 is an effective chemotherapy regimen in patients with GCT with no treatment-related deaths and a majority of patients requiring only 3 months of treatment.

Bone calcium/phosphorus ratio determination using dual energy X-ray method.

Non-invasive dual energy methods have been used extensively on osteoporosis diagnosis estimating parameters, such as, Bone Mineral Density (BMD) and Bone Mineral Content (BMC). In this study, an X-ray dual energy method (XRDE) was developed for the estimation of the bone Calcium-to-Phosphorous (Ca/P) mass ratio, as a bone quality index. The optimized irradiation parameters were assessed by performing analytical model simulations. X-ray tube output, filter material and thickness were used as input parameters. A single exposure technique, combined with K-edge filtering, was applied. The optimal X-ray spectra were selected according to the resulted precision and accuracy values. Experimental evaluation was performed on an XRDE system incorporating a Cadmium Telluride (CdTe) photon counting detector and three bone phantoms with different nominal mass Ca/P ratios. Additionally, the phantoms' mass Ca/P ratios were validated with energy-dispersive X-ray spectroscopy (EDX). Simulation results showed that the optimum filter atomic number (Z) ranges between 57 and 70. The optimum spectrum was obtained at 100 kVp, filtered with Cerium (Ce), with a surface density of 0.88 g/cm(2). All Ca/P ratio measurements were found to be accurate to within 1.6% of the nominal values, while the precision ranged between 0.91 and 1.37%. The accuracy and precision values of the proposed non-invasive method contributes to the assessment of the bone quality state through the mass Ca/P ratio determination.

Dual Energy Method for Breast Imaging: A Simulation Study.

Dual energy methods can suppress the contrast between adipose and glandular tissues in the breast and therefore enhance the visibility of calcifications. In this study, a dual energy method based on analytical modeling was developed for the detection of minimum microcalcification thickness. To this aim, a modified radiographic X-ray unit was considered, in order to overcome the limited kVp range of mammographic units used in previous DE studies, combined with a high resolution CMOS sensor (pixel size of 22.5 µm) for improved resolution. Various filter materials were examined based on their K-absorption edge. Hydroxyapatite (HAp) was used to simulate microcalcifications. The contrast to noise ratio (CNR tc ) of the subtracted images was calculated for both monoenergetic and polyenergetic X-ray beams. The optimum monoenergetic pair was 23/58 keV for the low and high energy, respectively, resulting in a minimum detectable microcalcification thickness of 100 µm. In the polyenergetic X-ray study, the optimal spectral combination was 40/70 kVp filtered with 100 µm cadmium and 1000 µm copper, respectively. In this case, the minimum detectable microcalcification thickness was 150 µm. The proposed dual energy method provides improved microcalcification detectability in breast imaging with mean glandular dose values within acceptable levels.