Combined Strategies Enable Highly Selective Light Olefins and para-Xylene Production on Single Catalyst Bed.

Achieving multiple high-value-added chemical production through novel reaction processes and shape-selective catalytic strategy is the key to realizing efficient low-carbon catalytic processes. In this work, a methanol-toluene coreaction system was developed, and combined control strategies of reaction pathway guidance and shape-selective catalysis were applied for the successful production of light olefins and para-xylene on single HZSM-5 catalyst bed. Cofeeding toluene additionally provides reactive and flowing aromatic hydrocarbon pool species that change the dominant reaction pathway in the complex network of the methanol reaction on HZSM-5 and promote the formation of ethylene. For the first time, the key reaction intermediates methylmethylenecyclodiene are directly captured and identified by experimental and theoretical techniques. This helps to propose the catalytic cycle for the dominant generation of ethylene and, more importantly, enriches the methanol-to-hydrocarbons (MTH) chemistry and hydrocarbon pool mechanism. Furthermore, 0.4HZSM-5@S-1-CLD, an optimized HZSM-5 catalyst modified by the silicalite-1 epitaxial growth followed by silanization approach, realizes highly selective production of light olefins (especially ethylene) and para-xylene, while excellent reactant activity is maintained. This highly efficient coreaction route gives an important leading significance in synthesizing the raw materials for the polyolefin and polyester industries. The establishment of the combined control strategies provides a model for the joint production of multiple target chemicals in complex catalytic processes.

Thermal resistance effect on anomalous diffusion of molecules under confinement.

Diffusion is generally faster at higher temperatures. Here, a counterintuitive behavior is observed in that the movement of long-chain molecules slows as the temperature increases under confinement. This report confirms that this anomalous diffusion is caused by the "thermal resistance effect," in which the diffusion resistance of linear-chain molecules is equivalent to that with branched-chain configurations at high temperature. It then restrains the molecular transportation in the nanoscale channels, as further confirmed by zero length column experiments. This work enriches our understanding of the anomalous diffusion family and provides fundamental insights into the mechanism inside confined systems.

Recognizing the Minimum Structural Units Driving the Crystallization of SAPO-34 in a Top-Down Process.

Recognizing the structure and nature of the nuclei for zeolites crystallization on an atomic level is of great importance, which can provide guidance on the control of crystallization kinetics and the rational synthesis of zeolites. However, it remains a long-standing challenge due to the difficulty in characterization of amorphous precursor with limited crystal nuclei. Herein, a top-down synthesis system was designed for SAPO-34 molecular sieve and well investigated. A clear precursor solution with abundant SAPO-34 crystal nuclei was obtained under a depolymerization-dominant condition. The species in the liquid precursor were identified by FT-ICR MS, solid-state MAS NMR and atomic pair distribution function analyses. In combination with various designed experiments, it is revealed that both the formation of small species containing Si-O-Al bonds and reaching a certain concentration, is crucial for driving the crystallization of SAPO-34, rather than structural units with specific spatial conformation. This work provides an important understanding on the (pre)nucleation of SAPO-34 and sheds light on the synthesis control of SAPO molecular sieves.

Atomic Insight into the Local Structure and Microenvironment of Isolated Co-Motifs in MFI Zeolite Frameworks for Propane Dehydrogenation.

Embedding metal species into zeolite frameworks can create framework-bond metal sites in a confined microenvironment. The metals sitting in the specific T sites of zeolites and their crystalline surroundings are both committed to the interaction with the reactant, participation in the activation, and transient state achievement during the whole catalytic process. Herein, we construct isolated Co-motifs into purely siliceous MFI zeolite frameworks (Co-MFI) and reveal the location and microenvironment of the isolated Co active center in the MFI zeolite framework particularly beneficial for propane dehydrogenation (PDH). The isolated Co-motif with the distorted tetrahedral structure ({(≡SiO)2Co(HO-Si≡)2}, two Co-O-Si bonds, and two pseudobridging hydroxyls (Co···OH-Si) is located at T1(7) and T3(9) sites of the MFI zeolite. DFT calculations and deuterium-labeling reactions verify that the isolated Co-motif together with the MFI microenvironment collectively promotes the PDH reaction by providing an exclusive microenvironment to preactivate C3H8, polarizing the oxygen in Co-O-Si bonds to accept H* ({(≡SiO)CoHδ- (Hδ+O-Si≡)3}), and a scaffold structure to stabilize the C3H7* intermediate. The Co-motif active center in Co-MFI goes through the dynamic evolutions and restoration in electronic states and coordination states in a continuous and repetitive way, which meets the requirements from the series of elementary steps in the PDH catalytic cycle and fulfills the successful catalysis like enzyme catalysis.

Longitudinal change of Th1, Th2, and Th17 cells and their relationship between cognitive impairment, stroke recurrence, and mortality among acute ischemic stroke patients.

BACKGROUND: T-helper (Th) cells regulate immunity and inflammation, and modulate cognitive impairment in both cardio-cerebrovascular and neurological diseases. This study aimed to explore the correlation of longitudinal change of Th1/2/17 cells with cognitive impairment and prognosis in acute ischemic stroke (AIS). METHODS: Th1/2/17 cells were detected by flow cytometry in peripheral blood samples from 150 AIS patients at admission (baseline), Day (D)1, D3, and D7 after admission, and from 30 controls. Mini-Mental State Examination (MMSE) score among AIS patients at discharge was assessed. Stroke recurrence and mortality were evaluated. RESULTS: Th1 (p = 0.013) and Th17 cells (p < 0.001) but not Th2 cells (p = 0.105) were elevated in AIS patients versus controls. Th1 cells (p = 0.027) and Th17 cells (p < 0.001) but not Th2 cells (p = 0.227) were positively correlated with NIHSS score in AIS patients. Furthermore, Th1 and Th17 cells elevated from baseline to D3 and then decreased on D7 after AIS onset, while Th2 cells illustrated an opposite trend (all p < 0.001). Th17 cells on D1 (p = 0.011), D3 (p = 0.014), and D7 (p < 0.001) were correlated with lower MMSE score, and their levels on D3 (p = 0.033) and D7 (p = 0.004) were related to elevated cognitive impairment. Th1 and Th2 cells were not related to cognitive function (all p > 0.05). Additionally, Th17 cells at baseline, D1, D3, and D7 (all p < 0.05) were increased in recurrent patients versus non-recurrent patients, and in survived patients versus dead patients, but Th1 or Th2 cells did not vary (all p > 0.05). CONCLUSION: Th17 cells correlate with increased cognitive impairment, stroke recurrence, and mortality among AIS patients.

Frustrated Lewis Pair in Zeolite Cages for Alkane Activations.

The frustrated Lewis pair (FLP) concept in homogeneous catalysis was extended to heterogeneous catalysis via the supramolecular system of FLP between deprotonated zeolite framework oxygens and confined carbocations in methanol-to-olefin (MTO) reactions. In this FLP, the polymethylbenzenium (PMB+ ) functioned as the Lewis acid to accept an electron pair, and the deprotonated framework oxygen site acted as the Lewis base to donate an electron pair. This FLP theoretically demonstrated the ability to undergo H2 heterolysis and alkanes dehydrogenation, and this was further confirmed by gas chromatography-mass spectrometer (GC-MS) catalytic experiments inside FLP-containing chabazite zeolites. All these findings not only bring new recognition to the carbocation chemistry in zeolite cages but also put forward a new reaction pathway as one part of MTO reactions.

Creation of Al-Enriched Mesoporous ZSM-5 Nanoboxes with High Catalytic Activity: Converting Tetrahedral Extra-Framework Al into Framework Sites by Post Treatment.

ZSM-5 zeolite nanoboxes with accessible meso-micro-pore architecture and strong acid sites are important in relevant heterogeneous catalysis suffering from mass transfer limitations and weak acidities. Rational design of parent zeolites with concentrated and non-protective coordination of Al species can facilitate post-synthetic treatment to produce mesoporous ZSM-5 nanoboxes. In this work, a simple and effective method was developed to convert parent MFI zeolites with tetrahedral extra-framework Al into Al-enriched mesoporous ZSM-5 nanoboxes with low silicon-to-aluminium ratios of ≈16. The parent MFI zeolite was prepared by rapid ageing of the zeolite sol gel synthesis mixture. The accessibility to the meso-micro-porous intra-crystalline network was probed systematically by comparative pulsed field gradient nuclear magnetic resonance diffusion measurements, which, together with the strong acidity of nanoboxes, provided superb catalytic activity and longevity in hydrocarbon cracking for propylene production.

Manipulating the Interfacial Energetics of n-type Silicon Photoanode for Efficient Water Oxidation.

The photoanodes with heterojunction behavior could enable the development of solar energy conversion, but their performance largely suffers from the poor charge separation and transport process through the multiple interfacial energy levels involved. The question is how to efficiently manipulate these energy levels. Taking the n-Si Schottky photoanode as a prototype, the undesired donor-like interfacial defects and its adverse effects on charge transfer in n-Si/ITO photoanode are well recognized and diminished through the treatment on electronic energy level. The obtained n-Si/TiOx/ITO Schottky junction exhibits a highly efficient charge transport and a barrier height of 0.95 eV, which is close to the theoretical optimum for n-Si/ITO Schottky contact. Then, the holes extraction can be further facilitated through the variation of surface energy level, with the NiOOH coated ITO layer. This is confirmed by a 115% increase in surface photovoltage of the photoanodes. Eventually, an unprecedentedly low onset potential of 0.9 V (vs RHE) is realized for water oxidation among n-Si photoanodes. For the water oxidation reaction, the n-Si/TiOx/ITO/NiOOH photoanode presents a charge separation efficiency up to 100% and an injection efficiency greater than 90% at a wide voltage range. This work identifies the important role of interfacial energetics played in photoelectrochemical conversion.

Evaluation of Distal Hemodynamic Changes of Lower Extremity after Endovascular Treatment: Correlation between Measurements of Color-Coded Quantitative Digital Subtraction Angiography and Ankle-Brachial Index.

PURPOSE: To confirm the feasibility of using time-to-peak (TTP) measurements derived from color-coded digital subtraction angiography (ccDSA) imaging to assess improvements in distal circulation in relation to the ankle-brachial index (ABI). MATERIALS AND METHODS: Nineteen patients who underwent percutaneous transluminal angioplasty and/or stent placement (in 20 lower extremities) were evaluated. A region of interest (ROI) at the proximal superficial femoral artery (SFA) was selected for a reference TTP for quantitative assessments. The ROI measurements of the TTP interval between medial and lateral plantar/dorsalis pedis relative to the reference was regarded as the ΔTTP and used to assess distal hemodynamic improvement achieved by the revascularization. The ABI was obtained with a handheld Doppler ultrasound machine with a manually operated blood-pressure cuff. Correlation between the two methods was analyzed. RESULTS: The ABI improved significantly from 0.44 ± 0.18 to 0.79 ± 0.20 (t = 10.11; P < .0001) after the intervention. TTP, which reflected the blood flow time from the proximal SFA to the foot, became much faster, from 11.86 seconds ± 4.26 to 6.75 seconds ± 2.03 (t = 6.57; P < .001). A good correlation was observed between the improvement ratios of ΔTTP and ABI (r = 0. 863). CONCLUSIONS: TTP measurements derived from ccDSA provide an easy and objective method for assessment of distal hemodynamic changes after endovascular treatment of lower-extremity peripheral arterial disease (PAD). It may provide a quantitative method to assess the adequacy of endovascular interventions and provide more objective suggestions for procedure endpoints, with potentially better clinical outcomes for patients with PAD.

Hepatic blood volume imaging with the use of flat-detector CT perfusion in the angiography suite: comparison with results of conventional multislice CT perfusion.

PURPOSE: To prospectively determine the feasibility of flat-detector (FD) computed tomography (CT) perfusion to measure hepatic blood volume (BV) in the angiography suite in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Twenty patients with HCC were investigated with conventional multislice and FD CT perfusion. CT perfusion was carried out on a multislice CT scanner, and FD CT perfusion was performed on a C-arm angiographic system, before transarterial chemoembolization procedures. BV values of conventional and FD CT perfusion were measured within tumors and liver parenchyma. The arterial perfusion portion of CT perfusion BV was extracted from CT perfusion BV by multiplying it by a hepatic perfusion index. Relative values (RVs) for CT perfusion arterial BV and FD CT perfusion BV (FD BV) were defined by dividing BV of tumor by BV of parenchyma. Relationships between BV and RV values of these two techniques were analyzed. RESULTS: In all patients, both perfusion procedures were technically successful, and all 33 HCCs larger than 10 mm were identified with both imaging methods. There were strong correlations between the absolute values of FD BV and CT perfusion arterial BV (tumor, r = 0.903; parenchyma, r = 0.920; both P < .001). Bland-Altman analysis showed a mean difference of -0.15 ± 0.24 between RVs for CT perfusion arterial BV and FD BV. CONCLUSIONS: The feasibility of FD CT perfusion to assess BV values of liver tumor and surrounding parenchyma in the angiographic suite was demonstrated.

A hematite photoanode with gradient structure shows an unprecedentedly low onset potential for photoelectrochemical water oxidation.

Ultra-high onset potential hinders the application of hematite for photoelectrochemical (PEC) water splitting. Herein, a hematite photoanode with an unprecedentedly low onset potential of 0.50 V vs. the reversible hydrogen electrode for PEC water oxidation is reported. The drastically reduced onset potential is mainly ascribed to the passivation of the hematite surface states and the gradient structure made by H2-O2 flame at high temperature.

An integrated photoelectrochemical-chemical loop for solar-driven overall splitting of hydrogen sulfide.

Abundant and toxic hydrogen sulfide (H2 S) from industry and nature has been traditionally considered a liability. However, it represents a potential resource if valuable H2 and elemental sulfur can be simultaneously extracted through a H2 S splitting reaction. Herein a photochemical-chemical loop linked by redox couples such as Fe(2+) /Fe(3+) and I(-) /I3 (-) for photoelectrochemical H2 production and H2 S chemical absorption redox reactions are reported. Using functionalized Si as photoelectrodes, H2 S was successfully split into elemental sulfur and H2 with high stability and selectivity under simulated solar light. This new conceptual design will not only provide a possible route for using solar energy to convert H2 S into valuable resources, but also sheds light on some challenging photochemical reactions such as CH4 activation and CO2 reduction.

A tantalum nitride photoanode modified with a hole-storage layer for highly stable solar water splitting.

Photoelectrochemical (PEC) water splitting is an ideal approach for renewable solar fuel production. One of the major problems is that narrow bandgap semiconductors, such as tantalum nitride, though possessing desirable band alignment for water splitting, suffer from poor photostability for water oxidation. For the first time it is shown that the presence of a ferrihydrite layer permits sustainable water oxidation at the tantalum nitride photoanode for at least 6 h with a benchmark photocurrent over 5 mA cm(-2) , whereas the bare photoanode rapidly degrades within minutes. The remarkably enhanced photostability stems from the ferrihydrite, which acts as a hole-storage layer. Furthermore, this work demonstrates that it can be a general strategy for protecting narrow bandgap semiconductors against photocorrosion in solar water splitting.

Exploring the dietary strategies of phenylalanine: Improving muscle nutraceutical quality as well as muscle glycogen and protein deposition in adult grass carp (Ctenopharyngodon idella).

Muscle is the main edible part of bony fish. The purpose of this study was to investigate the influences of phenylalanine (Phe) on muscle quality, amino acid composition, fatty acid composition, glucose metabolism, and protein deposition in adult grass carp. The diets at 2.30, 4.63, 7.51, 10.97, 13.53, and 17.07 g/kg Phe levels were fed for 9 weeks. The results manifested that Phe (10.97-13.53 g/kg) increased the pH of the fillets and decreased muscle cooking loss and lactic acid content; Phe (7.51-17.07 g/kg) improved the composition of the fillets in terms of flavor (free) amino acids, bound amino acids (especially EAA), and fatty acids (especially EPA and DHA); Phe (7.51-13.53 g/kg) increased muscle glycogen content (possibly related to the AMPK signaling pathway) and muscle protein deposition (possibly related to IGF-1/4EBP1/TOR and AKT/FOXOs signaling pathways). In conclusion, a diet with appropriate Phe levels could improve fillet quality.

Effects of surface modification on photocatalytic activity of CdS nanocrystals studied by photoluminescence spectroscopy.

The surface features of semiconductors play very important roles in photocatalytic processes but they are far from being well understood. In this work, we used CdS nanocrystals (NCs) as a model semiconductor photocatalyst to investigate the influence of surface features on photocatalytic activity. The effects of surface modification on the recombination behavior were studied by photoluminescence (PL) spectroscopy. The surface of CdS NCs was modified by tuning the surface S/Cd ratio or by co-loading with Pt and/or PdS co-catalysts. It was found that the surface modifications significantly affect the emission bands at ~540 nm due to shallow traps and ~650 nm assigned to S(2-) vacancies, and consequently the photocatalytic activities. Without co-catalysts loading, the excited carriers are readily transferred to the shallow traps, while they are readily transferred to the co-catalysts upon co-catalysts loading. These results demonstrate that the surface features are crucial to photocatalytic activity of the CdS NCs. The surface modification is helpful for the excited carriers to transfer to either the shallow trap states or co-catalysts, resulting in higher quantum efficiency of photocatalytic H(2) production.

Reminiscence therapy is a feasible care program for improving cognitive function, anxiety, and depression in recurrent acute ischemic stroke patients: a randomized, controlled study.

OBJECTIVE: Reminiscence therapy provides benefits among first-episode acute ischemic stroke (AIS) patients and their caregivers. This study intended to further compare the effect of reminiscence therapy plus usual care (RTUC) and usual care (UC) on cognitive function, anxiety, and depression among recurrent AIS patients. METHODS: Totally, 160 recurrent AIS patients were enrolled and randomized in a 1:1 ratio into the RTUC group (N = 81) and UC group (N = 79), then a 12-month corresponding intervention was conducted in each group. Mini-Mental State Examination (MMSE) score and Hospital Anxiety and Depression Scale (HADS) were evaluated on discharge (M0), at month (M) 3, M6, M9, and M12 after discharge. RESULTS: MMSE scores at M6 (27.0 ± 1.6 vs. 26.3 ± 2.3, P = 0.031) and M12 (27.0 ± 1.7 vs. 26.1 ± 2.4, P = 0.009) were elevated, while cognitive impairment rate at M12 (29.2% vs. 45.7%, P = 0.042) and cognitive impairment severity at M12 (P = 0.029) were declined in RTUC group compared to UC group. Meanwhile, the HADS-anxiety scores at M9 (5.7 ± 3.1 vs. 6.9 ± 4.0, P = 0.046) and M12 (5.6 ± 2.7 vs. 7.0 ± 4.3, P = 0.024), anxiety rate at M12 (22.2% vs. 38.2%, P = 0.039) and anxiety severity at M12 (P = 0.018) were declined in RTUC group compared to UC group. Besides, the HADS-depression score at M12 (5.7 ± 3.1 vs. 6.8 ± 3.3, P = 0.043) was decreased in RTUC group compared to UC group, but depression rate and severity were not different between the two groups at each visit point (all P > 0.05). CONCLUSION: RTUC program elevates cognitive functions and alleviates mental problems in recurrent AIS patients.

Propofol via Antioxidant Property Attenuated Hypoxia-Mediated Mitochondrial Dynamic Imbalance and Malfunction in Primary Rat Hippocampal Neurons.

BACKGROUND: Hypoxia may induce mitochondrial abnormality, which is associated with a variety of clinical phenotypes in the central nervous system. Propofol is an anesthetic agent with neuroprotective property. We examined whether and how propofol protected hypoxia-induced mitochondrial abnormality in neurons. METHODS: Primary rat hippocampal neurons were exposed to propofol followed by hypoxia treatment. Neuron viability, mitochondrial morphology, mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential (MMP), and adenosine triphosphate (ATP) production were measured. Mechanisms including reactive oxygen species (ROS), extracellular regulated protein kinase (ERK), protein kinase A (PKA), HIF-1α, Drp1, Fis1, Mfn1, Mfn2, and Opa1 were investigated. RESULTS: Hypoxia increased intracellular ROS production and induced mPTP opening, while reducing ATP production, MMP values, and neuron viability. Hypoxia impaired mitochondrial dynamic balance by increasing mitochondrial fragmentation. Further, hypoxia induced the translocation of HIF-1α and increased the expression of Drp1, while having no effect on Fis1 expression. In addition, hypoxia induced the phosphorylation of ERK and Drp1ser616, while reducing the phosphorylation of PKA and Drp1ser637. Importantly, we demonstrated all these effects were attenuated by pretreatment of neurons with 50 µM propofol, antioxidant α-tocopherol, and ROS scavenger ebselen. Besides, hypoxia, propofol, α-tocopherol, or ebselen had no effect on the expression of Mfn1, Mfn2, and Opa1. CONCLUSIONS: In rat hippocampal neurons, hypoxia induced oxidative stress, caused mitochondrial dynamic imbalance and malfunction, and reduced neuron viability. Propofol protected mitochondrial abnormality and neuron viability via antioxidant property, and the molecular mechanisms involved HIF-1α-mediated Drp1 expression and ERK/PKA-mediated Drp1 phosphorylation.

The effect of propofol on hypoxia- and TNF-α-mediated BDNF/TrkB pathway dysregulation in primary rat hippocampal neurons.

AIMS: Hypoxia and inflammation may lead to BDNF/TrkB dysregulation and neurological disorders. Propofol is an anesthetic with neuroprotective properties. We wondered whether and how propofol affected BDNF/TrkB pathway in hippocampal neurons and astrocytes. METHODS: Primary rat hippocampal neurons and astrocytes were cultured and exposed to propofol followed by hypoxia or TNF-α treatment. The expression of BDNF and the expression/truncation/phosphorylation of TrkB were measured. The underlying mechanisms were investigated. RESULTS: Hypoxia and TNF-α reduced the expression of BDNF, which was reversed by pretreatment of 25 µM propofol in hippocampal neurons. Furthermore, hypoxia and TNF-α increased the phosphorylation of ERK and phosphorylation of CREB at Ser142, while reduced the phosphorylation of CREB at Ser133, which were all reversed by 25 µM propofol and 10 µM ERK inhibitor. In addition, hypoxia or TNF-α did not affect TrkB expression, truncation, or phosphorylation in hippocampal neurons and astrocytes. However, in hippocampal neurons, 50 µM propofol induced TrkB phosphorylation, which may be mediated by p35 expression and Cdk5 activation, as suggested by the data showing that blockade of p35 or Cdk5 expression mitigated propofol-induced TrkB phosphorylation. CONCLUSIONS: Propofol modulated BDNF/TrkB pathway in hippocampal neurons via ERK/CREB and p35/Cdk5 under the condition of hypoxia or TNF-α exposure.

Clinical evaluation of volume of interest imaging combined with metal artifact reduction reconstruction techniques in coiling and stent assisted coiling during neurointerventional procedures.

PURPOSE: Three-dimensional (3D) scans with flat detector angiographic systems are widely used for neurointerventions by providing detailed vascular information. However, its associated radiation dose and streak metal artifact generated by implanted treatment devices remain issues. This work evaluates the feasibility and clinical value of volume of interest imaging combined with metal artifact reduction (VOI+MAR) to generate high quality 3D images with reduced radiation dose and metal artifacts. MATERIAL AND METHODS: Full volume (FV) and VOI scans were acquired in 25 patients with intracranial aneurysms and treated with either endovascular coiling (n=9) or stent assisted coiling (n=16) procedures. FV and VOI scans were reconstructed with conventional syngo DynaCT and VOI +MAR prototype software, respectively. RESULTS: Quantitative evaluation results demonstrated that compared with standard FV syngo DynaCT images, overall image quality was improved in the VOI+MAR reconstructed images, with streak metal artifacts considerably reduced or even removed; details of soft tissue in the vicinity of the metal devices was well preserved or recovered in the majority of cases. Radiation dose to patients calculated by dose area product was found to be significantly reduced using VOI scans. CONCLUSION: This study confirmed the feasibility of using VOI+MAR prototype software to achieve high image quality of a small volume of clinical interest and to reduce radiation dose. This technique has potential to improve patient safety and treatment outcomes.

Computer-aided evaluation of anatomical accuracy of image fusion between X-ray CT and SPECT.

Hybrid scanners, which enable the performance of single photon emission computed tomography (SPECT) and X-ray computed tomography (CT) in one imaging session, have considerable diagnostic potential. However, evaluating the anatomical accuracy of image fusion inherent to these systems remains a challenge. This paper proposes a method for evaluating this variable with minimum user interaction. It focuses on measuring the distance between the centers of gravity of the SPECT hot spot and its counterpart in the CT image. A localized maximally stable extremal regions method is proposed to automatically segment SPECT hot spots, while the corresponding CT structures are segmented by the semi-automatic random walk method, based on a fast multigrid solver. Accuracy and reproducibility of the validation method have been preliminary confirmed by the test with 21 clinical data-sets.