Whole-brain Optical Imaging: A Powerful Tool for Precise Brain Mapping at the Mesoscopic Level / 神经科学通报·英文版

The mammalian brain is a highly complex network that consists of millions to billions of densely-interconnected neurons. Precise dissection of neural circuits at the mesoscopic level can provide important structural information for understanding the brain. Optical approaches can achieve submicron lateral resolution and achieve "optical sectioning" by a variety of means, which has the natural advantage of allowing the observation of neural circuits at the mesoscopic level. Automated whole-brain optical imaging methods based on tissue clearing or histological sectioning surpass the limitation of optical imaging depth in biological tissues and can provide delicate structural information in a large volume of tissues. Combined with various fluorescent labeling techniques, whole-brain optical imaging methods have shown great potential in the brain-wide quantitative profiling of cells, circuits, and blood vessels. In this review, we summarize the principles and implementations of various whole-brain optical imaging methods and provide some concepts regarding their future development.

A single-center, retrospective analysis of relapse and progression patterns of primary central nervous system lymphoma: can whole brain radiotherapy be replaced? / 南方医科大学学报

OBJECTIVE@#To analyze recurrence and progression patterns of primary central nervous system lymphoma (PCNSL) in patients without whole brain radiotherapy (WBRT) and assess the value of WBRT in PCNSL treatment.@*METHODS@#This retrospective single-center study included 27 patients with PCNSL, who experienced recurrence/progression after achieving complete remission (CR), partial remission, or stable disease following initial treatments with chemotherapy but without WBRT. The patients were followed up regularly after the treatment for treatment efficacy assessment. By comparing the anatomical location of the lesions on magnetic resonance images (MRI) at the initial diagnosis and at recurrence/progression, we analyzed the patterns of relapse/progression in patients with different treatment responses and different initial status of the lesions.@*RESULTS@#MRI data showed that in 16 (59.26%) of the 27 patients, recurrence/progression occurred in out-field area (outside the simulated clinical target volume [CTV]) but within the simulated WBRT target area in 16 (59.26%) patients, and within the CTV (in-field) in 11 (40.74%) patients. None of the patients had extracranial recurrence of the tumor. Of the 11 patients who achieved CR after the initial treatments, 9 (81.82%) had PCNSL recurrences in the out-field area but within WBRT target area; of the 13 patients with a single lesion at the initial treatment, 11 (84.62%) experienced PCNSL recurrence in the out-field area but within WBRT target area.@*CONCLUSIONS@#Systemic therapy combined with WBRT still remains the standard treatment for PCNSL patients, especially those who achieve CR after treatment or have a single initial lesion. Future prospective studies with larger sample sizes are needed to further explore the role of low-dose WBRT in PCNSL treatment.

A preliminary study of fecal microbiota transplantation alleviating inhibition of radiation-induced hippocampal neurogenesis in mice / 中华放射肿瘤学杂志

Objective:To evaluate the effects of whole brain irradiation (WBI) and fecal microbiota transplantation (FMT) on hippocampal neurogenesis and the composition of gut microbiota in mice.Methods:Forty specific pathogen free ICR male mice (8-week-old, weighed 30 g) were divided into four groups by simple random sample method: control group (group C), radiation group (group R), group C+FMT and group R+FMT, 10 in each group. Animal models were established by WBI at a dose of 10 Gy by 4 MeV electron beam. In group C+FMT and group R+FMT, mice were gavaged with normal fecal bacteria suspension on day 2 post-irradiation, while those in group C and group R were gavaged with phosphate buffered saline as alternative. Hippocampal tissues and feces in four groups were collected on day 15 post-irradiation. 16S rRNA sequencing was used to detect the species and abundance of fecal flora. BrdU +/NeuN + immunofluorescence staining was performed to observe the neurogenesis in hippocampus of mice. Results:WBI and FMT had no effect on survival rate and body weight of mice. WBI induced the inhibition of hippocampal neurogenesis and flora disorder. The quantity of Bacteroideae and Rumen bacteria was increased by 28.6% and 102.9%, whereas that of Lactobacillus was significantly decreased by 70.6% ( P<0.05). FMT regulated the abundance of bacteria. The abundance of Enterobacteriaceae was significantly declined by 65.1% ( P=0.028), while that of Lactobacillus was increased by 58.2% ( P=0.015). FMT also promoted hippocampal neurogenesis to some extent after WBI. Conclusions:This preliminary study demonstrates that FMT alleviates the inhibition of hippocampal neurogenesis and flora disorder induced by WBI in mice. Ionizing radiation directly acting on the whole brain of mice indirectly disturbs the composition of gut microbiota, which in turn affects the degree of hippocampal neurogenesis in the brain of mice. There is a bidirectional interaction between gut microbiota and brain.

Recent advances in hippocampal sparing whole brain radiotherapy / 中华放射肿瘤学杂志

Whole brain radiotherapy (WBRT) is the standard radiotherapy regimen of preventive radiation for patients diagnosed with brain metastases and non-small cell lung cancer, which can improve intracranial control and prolong overall survival. However, neurocognitive functions (NCF) decline due to impaired hippocampal might occur thereafter. Recent studies have shown that hippocampal sparing WBRT (HS-WBRT) is capable of protecting neurocognitive function and improving quality of life (QOL). In this review, the authors described the methods and significance of hippocampal sparing, summarized the research progress on clinical trials related to HS-WBRT in combination with the development of radiotherapy technology and experimental drugs, and discussed the existing controversies and problems, aiming to provide reference for clinical work.

Clinical application of LinaTech linear accelerator VenusX to hippocampal protection in whole-brain radiotherapy / 中华放射医学与防护杂志

Objective:To compare the dosimetric differences between the VenusX accelerator with an orthogonal dual-layer multi-leaf collimator (MLC) and the Varian′s CLINAC IX and EDGE accelerators with a single-layer MLC for hippocampus protection in the whole-brain radiotherapy (WBRT).Methods:Forty patients with multiple brain metastases admitted to the Radiotherapy Department of the Shanghai General Hospital from June 2021 to February 2023 were selected in this study. Three whole-brain treatment plans were designed based on the above three accelerators for each patient. Under the same prescription dose, radiation field, and plan constraints, the three plans were compared in terms of the dosimetric differences in target volumes, hippocampi, and adjacent organs at risk (OARs), as well as the execution efficiency.Results:For the planning target volume (PTV), there were statistically significant differences in approximate maximum dose ( D2) between the VenusX and IX plans ( t = 4.94, P < 0.05), in approximate minimum dose ( D98) between the VenusX and EDGE plans ( t = 5.98, P < 0.05), in the target conformity indices (CIs) between VenusX plan and EDGE plans, and between the VenusX and IX plans ( t = -6.84, -14.30; P < 0.05), and dose homogeneity indices (HIs) between the VenusX and IX plans ( t = 3.48, P < 0.05). For OARs, the maximum doses ( Dmax) and average doses ( Dmean) to bilateral hippocampi of the VenusX plan were lower than those of the EDGE and IX plans ( t = 8.59-17.11, P < 0.05); the maximum doses ( Dmax) to bilateral lenses, bilateral optic nerves, and optic chiasma of the VenusX plan were lower than those of the other two plans ( t = 2.10-20.80, P < 0.05); and the differences between the maximum doses ( Dmax) to the brain stem of the VenusX and EDGE plans were statistically significant ( t = 3.86, P < 0.05). In terms of plan execution efficiency, the number of machine jumps (MU) and the treatment time of the VenusX plan were higher than those of the EDGE and IX plans, with statistically significant differences ( t = -56.48, -56.90, P < 0.05). Conclusions:The doses to target volumes of the three treatment plans all meet the prescription requirements, and the VenusX plan outperforms the EDGE and IX plans in the protection of OARs. Despite the reduced execution efficiency, the VenusX plan shortens the actual treatment time by improving the dosage rate, thus meeting the clinical requirements.

Clinical experience of off-pump arch branches preferential reconstruction and whole brain perfusion in the treatment of type A / 中华胸心血管外科杂志

Objective:To introduce the early results of total aortic arch replacement (TAA) without cardiopulmonary bypass (CPB) and without interruption of cerebral blood supply, using the technique of arch branches preferential reconstruction and whole brain perfusion for brain protection.Methods:Between June 2020 and March 2021, a total of 9 Stanford type A aortic dissection patients we performed total arch replacement by using the technique of arch branches preferential reconstruction and whole brain perfusion without cardiopulmonary bypass and without interruption of blood supply to the brain. The method of this reconstruction technique is as follows: A 24F aortic cannula was inserted into the true lumen at the root of the transverse innominate artery (IA) to connect one end of the artery for cardiopulmonary bypass. The access was connected to 14F artery via Y-connector and inserted into IA cavity to maintain blood supply to brain. Without cardiopulmonary bypass, the 10 mm branch of the four branch artificial blood vessel was anastomosed with the innominate artery IA. The perfusion collateral was connected to the second end of the artery of CPB (single pump and double tubes) to continue to supply blood for IA. The left common carotid artery (LCA) and left subclavian artery (LSCA) were reconstructed by the same method. When IA and LCA were anastomosed, the distal blood supply was not interrupted. After the three branches of the aortic arch were anastomosed, we started to turn the machine, then cooled down and blocked the ascending aorta to further complete the operation of the aortic root and arch. During the period of lower body circulatory arrest, the whole brain was perfused with low flow.Results:No intraoperative death or perioperative complications occurred in all patients, and they were discharged smoothly. The cardiopulmonary bypass time was (192.4±58.1) min, the aortic clamping time was (128.3±52.4) min, the lower body circulatory arrest time was (29.1±1.3) min, and the postoperative awake time was (8.2±3.7) h.Conclusion:Off-pump arch branches preferential reconstruction can provide physiological whole brain perfusion, shorten the cardiopulmonary bypass time and aortic occlusion time, and the operation is safe and effective.

Advances in Treatment of Brain Metastasis from Lung Cancer / 肿瘤防治研究

Lung cancer is the malignant tumor with the highest incidence and mortality in China, and is prone to brain metastasis in the process of disease development, which seriously affects the quality of life and survival of patients. The treatment methods for brain metastasis of lung cancer include surgery, chemotherapy, whole brain radiotherapy, stereotactic radiosurgery, molecular targeted therapy, immunotherapy, anti-angiogenesis therapy, etc. It's one of the research hotspots to choose reasonable and effective treatment schemes for different patients. This paper reviews the research progress in the treatment of brain metastasis from lung cancer, to provide reference for selecting more reasonable clinical treatment for the patients.

Dosimetric comparison of hippocampal avoidance wholebrain radiotherapy with flattening filter and flattening filter-free modes / 中国辐射卫生

@#<b>Objective</b> To compare the dosimetric differences of volumetric modulated arc therapy (VMAT) with flattening filter(FF) and flattening filter-free(FFF) modes in hippocampal avoidance whole brain radiotherapy. <b>Methods</b> We included 15 patients with hippocampal-sparing whole brain radiotherapy, and designed two radiotherapy plans of FF-VMAT and FFF-VMAT for each patient. On the premise of meeting clinical dose requirements, the two plans’ dosimetry, total number of monitor units, and beam-on time were compared. <b>Results</b> There were no significant differences in the target coverage, conformity index, and dose gradient of the FF-VMAT and FFF-VMAT plans (<i>P</i> > 0.05). The <i>D</i>_max, <i>D</i>_100%, and <i>D</i>_meanto the hippocampal tissue were significantly lower with FFF-VMAT [(15.13 ± 0.38) Gy, (7.12 ± 0.34) Gy, and (9.76 ± 0.43) Gy, respectively)] than with FF-VMAT (16.46 ± 0.56) Gy, (7.72 ± 0.28) Gy, and (10.54 ± 0.48) Gy, respectively)] (<i>P</i> < 0.05). The <i>D</i>_maxto the left and right lenses and the <i>D</i>_meanto the left and right eyeballs with FFF-VMAT were (7.26 ± 0.43) Gy, (6.29 ± 1.13) Gy, (11.01 ± 0.94) Gy, and (9.78 ± 1.13) Gy, respectively, which were significantly lower than FF-VMAT’s corresponding doses of (8.09 ± 0.66) Gy, (7.80 ± 0.74) Gy, (11.38 ± 1.09) Gy, and (11.05 ± 0.90) Gy, respectively (<i>P</i> < 0.05). The doses to other organs at risk including the optic nerve and optic chiasm were all controlled within the safe dosage ranges, with no significant differences between the two plans (<i>P</i> > 0.05). The FFF-VMAT plan had a significantly greater number of monitor units and a significantly shorter beam-on time than the FF-VMAT plan (<i>P</i> < 0.05). <b>Conclusion</b> Both FF-VMAT and FFF-VMAT can meet the clinical requirements, with FFF-VMAT having better hippocampus and lens protection, shorter beam-on time, and higher treatment efficiency.

Clinical characteristics, management, and outcome of gestational trophoblastic neoplasia patients with brain metastasis: A 10-year experience at the Philippine General Hospital / Philippine Journal of Obstetrics and Gynecology

Objective@#This study aimed to determine the clinical characteristics, management, and outcome of gestational trophoblastic neoplasia (GTN) patients with brain metastasis.@*Materials and Methods@#This was a 10‑year descriptive study that included all patients with brain metastasis from GTN. Patients’ sociodemographic and clinicopathological profiles were described. Using Kaplan–Meier survival curve, the survival time was determined@*Results@#From January 1, 2010, to December 31, 2019, there were 33 GTN patients with brain metastasis. Four were excluded from the study due to incomplete records. Twenty‑nine patients were included in the study. Nineteen (65.51%) patients presented with neurologic symptoms upon diagnosis and one (3.44%) during treatment. All received etoposide, methotrexate, actinomycin, oncovin (EMACO) as first‑line treatment. Five (17.24%) patients were given induction chemotherapy with low‑dose etoposide–cisplatin. Seventeen (58.62%) patients underwent whole‑brain radiation and two (6.89%) were given intrathecal methotrexate. Thirteen patients (44.82%) achieved biochemical remission with EMACO chemotherapy. Four patients (13.79%) had resistance to EMACO and were given Etoposide Cisplatin Etoposide Methotrexate Actinomycin (EP EMA). Four patients (13.79%) underwent an adjunctive hysterectomy. Four patients (13.79%) died during treatment. One patient (3.44%) was unable to continue her chemotherapy because she got pregnant before her first consolidation course. There were eight early deaths (<4 weeks of admission) and hence were excluded in the analysis. Three patients who went into biochemical remission relapsed on the 1st, 2nd, and 3rd months after their last consolidation course, respectively. The median follow‑up time was 27 months. After excluding early deaths, the survival rate between 3 and 7 years after treatment is at 61.9%. The mean survival time was 5.43 years. Six surviving patients were contacted. Five (17.24%) of them had resumed their everyday life, and one is currently undergoing chemotherapy.@*Conclusion@#The study was able to document brain metastasis from GTN to be 14.28% (29/203) among metastatic high‑risk admissions. The biochemical remission rate from first‑line treatment was of 61.90% (13/21) and resistance rate was 19.04% (4/21). Lost to follow up after achieving biochemical remission was a challenge encountered

Progress on radiotherapy of primary central nervous system lymphoma / 中华放射肿瘤学杂志

Primary central nervous system lymphoma (PCNSL) is a rare aggressive non-Hodgkin′s lymphoma that occurs in the brain, spinal cord, meninges or eyes. Diffuse large B-cell lymphoma accounts for the vast majority, of which non-GCB subtype is more common. The median survival time of untreated patients is only 3 months. Surgical removal of the tumor alone has no obvious survival benefit. Early single use of whole brain radiation therapy (WBRT) yields a high remission rate, but the duration is short, and delayed neurotoxicity is an important complication, especially for elderly patients. Subsequent studies found that high-dose methotrexate-based chemotherapy combined with WBRT significantly improved the prognosis of this disease. However, combination therapy increases the risk of neurotoxicity, and this strategy has been questioned. In recent years, reduced-dose WBRT and autologous hematopoietic stem cell transplantation have gradually replaced the previous standard-dose WBRT. This article reviews the progress on the radiotherapy for PCNSL.

Prognostic analysis of patients with brain metastases from non-small cell lung cancer treated with different doses of whole brain radiotherapy / 中华放射肿瘤学杂志

Objective:To analyze the prognosis and influencing factors of patients with brain metastases from non-small cell lung cancer (NSCLC) treated with different doses of whole brain radiotherapy (WBRT).Methods:A total of 244 NSCLC patients with brain metastases who underwent WBRT in the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different doses of WBRT (EQD 2Gy), they were divided into the 30-39 Gy group ( n= 104) and ≥40 Gy group ( n= 140). The intracranial progression-free survival (iPFS) and overall survival (OS) were compared betweentwo groups. According to the number of brain metastases, GPA score, KPS score, chemotherapy and targeted therapy, the prognosis of different doses of WBRT was further analyzed. Results:The median iPFS and OS of all patients were 6.9 months and 11.8 months, respectively. Univariate survival analysis: the 1-year iPFS and 1-year OS between two groups were 22.5% and 25.4%( P=0.430) and 41.1% and 46.4%( P=0.068), respectively. Multivariate survival analysis: different doses of WBRT were not associated with the improvement of iPFS and OS; independent factors influencing iPFS included local boost, gender, number of brain metastases, chemotherapy and targeted therapy; independent factors influencing OS included gender, number of brain metastases, chemotherapy and targeted therapy. Subgroup analysis: in patients with KPS≥90, the 1-year iPFS and OS of patients with WBRT ≥ 40 Gy were seemingly better than those of their counterparts with 30-39 Gy, but the difference was statistically significant only in OS ( P=0.047), the difference was not statistically significant in iPFS ( P=0.068); in patients with chemotherapy, the 1-year iPFS and OS of patients with WBRT≥40 Gy were better than those of their counterparts with 30-39 Gy ( P=0.017, P=0.012); in patients with targeted therapy, the 1-year iPFS and OS in the WBRT≥40 Gy group were better than those in the 30-39 Gy group ( P=0.012, P=0.045). Conclusions:The 30-39 Gy may be the appropriate dose of WBRT for NSCLC patients with brain metastases. WBRT≥40 Gy does not bring more benefits. WBRT≥40 Gy may benefit NSCLC patients with brain metastases with high KPS score or active systemic therapy.

Prognostic analysis of patients with brain metastases from non-small cell lung cancer treated with supplemental radiotherapy under different prognostic scores / 中华放射肿瘤学杂志

Objective:To analyze the prognosis and influencing factors of different radiotherapy modes in patients with brain metastases from non-small cell lung cancer (NSCLC), and to explore the best benefit population with radiotherapy boost under different prognostic scores.Methods:634 patients with brain metastasis from NSCLC admitted to the Fourth Hospital of Hebei Medical University from 2013 to 2015 were analyzed retrospectively. According to different radiotherapy modes, they were divided into three groups: no radiotherapy group ( n=330), whole-brain radiotherapy group (WBRT)( n=127) and whole-brain radiotherapy combined with boost group (WBRT+ boost)( n=177). The intracranial progression-free survival (iPFS) and overall survival (OS) were calculated by Kaplan-Meier method. The multivariate prognostic factors were analyzed by the Cox models. Results:The median iPFS and OS of all patients were 6.9 months and 9.0 months, respectively. In the no radiotherapy, WBRT and WBRT+ boost groups, the 1-year iPFS was 15.1%, 16.3% and 40.2%( P=0.002), and the 1-year OS was 33.7%, 38.2% and 48.1%( P<0.001), respectively. Multivariate survival analysis demonstrated that different radiotherapy modes were the independent factors affecting iPFS and OS. Subgroup analysis revealed that for patients with 1-3 brain metastases, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone ( P=0.026, P=0.044) when GPA score was 2.5-4.0; the 1-year OS and iPFSin the WBRT+ boost group were better than those of WBRT alone ( P=0.036, P=0.049) when there was no targeted therapy; for patients with ≥4 brain metastases, the 1-year iPFS in the WBRT+ boost group was better than that of WBRT alone ( P=0.019, P=0.012) when GPA score was 2.5-4.0 and there was no targeted therapy. When the GPA score was 0-2 or there was targeted therapy, the 1-year OS and iPFS in the WBRT+ boost group were better than those of WBRT alone, but the difference was not statistically significant (all P>0.05). Conclusions:Radiotherapy can significantly improve the iPFS and OS of NSCLC patients with brain metastases. When the number of brain metastases is 1-3, GPA score is 2.5-4.0 or no targeted therapy, boost may improve the iPFS and OS; when the number of brain metastases is more than 4, GPA score is 2.5-4.0 or no targeted therapy, boost may only bring iPFS benefit; when GPA score is 0-2 or targeted therapy, boost may not benefit significantly.

The impact of whole brain radiation therapy on overall survival in patients with extensive stage small cell lung cancer with brain metastases / 中华放射肿瘤学杂志

Objective:To evaluate whether whole brain radiation therapy(WBRT) could benefit small cell lung cancer (SCLC) patients with brain metastases.Methods:Clinical data of 245 patients who were diagnosed with extensive stage SCLC with brain metastases admitted to our hospital from 2010 to 2020 were retrospectively analyzed. Among them, 168 patients received WRBT (WBRT group, radiation dose: 30Gy in 10 fractions), and 77 patients did not receive WBRT (non-WBRT group). All patients received 4-6 cycles of chemotherapy, and the chemotherapy regimen included cisplatin (or carboplatin) plus etoposide. One hundred and fifteen patients received thoracic radiotherapy. The endpoint was overall survival after brain metastases(BM-OS). Chi-square test was used to compare categorical data, and stabilized inverse probability of treatment weighting(sIPTW) was used to match the factors between WBRT and no-WBRT groups. Survival analysis was estimated by Kaplan-Meier method, and the log-rank test was used to compare survival curves between two groups. Results:The median BM-OS for the whole group of patients was 9.1 months, and 10.6 months and 6.7 months in the WBRT and non-WBRT groups, respectively( P=0.003). After balanced influencing factors with stabilized sIPTW, significant difference still existed in BM-OS between two groups( P=0.02). In 118 patients with synchronous brain metastases, the median BM-OS in two groups were 13.0 months and 9.6 months( P=0.007); and in 127 patients with metachronous brain metastases, the median BM-OS were 8.0 months and 4.1 months( P=0.003). In 50 patients without extracranial metastases, the median BM-OS were 13.3 months and 10.9 months( P=0.259)in two groups; while in 195 patients with extracranial metastases, the median BM-OS were 9.5 months and 5.9 months( P=0.009)in two groups. Conclusions:WBRT could prolong the OS in extensive stage SCLC patients with brain metastases.

Chronic intermittent hypobaric hypoxia improved the memory and cognitive impairment of mice with whole brain irradiation / 中华放射医学与防护杂志

Objective:To observe the changes in hippocampus (CA1) and study the effect of chronic intermittent hypobaric hypoxia (CIHH) preconditioning on the memory and cognitive function of mice exposed to the whole brain irradiation.Methods:A total of 48 C57BL/6 male mice were randomly divided into control group, CIHH group, irradiation group (IR group) and CIHH+ IR group. For IR group, the whole brain of mice were irradiated with 10 Gy of 6 MV X-rays in a single fraction. Pretreatment with CIHH was performed by placing mice in a hypobaric chamber before radiation. The mirrors water maze experiment was performed in the four groups to observe the escape latency, the number of crossing platforms and the target quadrant residence time. Nissl staining was used to observe the changes of neuronal cells in hippocampal CA1 region. Immunofluorescence was used to detect the expression of microtubule-associated protein cells (DCX) in the subgranular zone (SGZ) of hippocampal dentate gyrus (DG) to evaluate neurogenesis.Results:After 30 days of whole brain irradiation, the escape latency of mice prolonged gradually, the frequency of crossing platform decreased ( P< 0.001), and the exploration time in the target quadrant decreased ( P<0.001). X-ray irradiation caused disorder of mice neuronal cells, degeneration and necrosis of neuronal cells, and decrease of DCX expression in CA1 region of mice. Compared with IR group, the CIHH+ IR group had shortened the escape latency, increased the frequency of crossing platform [(2.08±0.26) vs. (0.83±0.24), P<0.001], and also increased the exploration time in the target quadrant [(14.12±0.82)s vs. (7.42±0.73)s, P<0.001]. Pretreatment with CIHH also alleviated the deformation and necrosis of neurons in hippocampus, and increased DCX expression in CA1 region. Conclusions:Pretreatment of mice with CIHH plays a protective role in radiation induced hippocampal injury.

Measurement of local consistency of the whole brain after aerobic exercise based on magnetic resonance imaging / Medição da consistência local de todo o cérebro após exercícios aeróbicos com base em imagens de ressonância magnética / Medición de la consistencia local de todo el cerebro después del ejercicio aeróbico basada en imágenes de resonancia magnética

ABSTRACT Introduction: The rapid development of rs-fMRI in recent years can provide new scientific evidence of the plasticity of the child's brain. Objective: To reveal the effect of short-term moderate-intensity aerobic exercise on local consistency of brain function in children at rest, and to provide new evidence for elucidating the relationship between physical exercise and plasticity of children's brain. Methods: Using resting state functional magnetic resonance imaging (rs-fMRI) technology and local consistency (ReHo) analysis method to detect a 30-min short-term moderate-intensity aerobic exercise before and after children's brain function local consistency changes; using the Flanker task measurement Changes in children's executive function before and after exercise. Results: 1) A 30-min short-term moderate-intensity aerobic exercise made the children's bilateral posterior buckle back, left dorsolateral prefrontal lobe, left frontal medial gyrus, bilateral central posterior gyrus, left suboccipital gyrus, and tongue gyrus. 2) A 30-minute short-term moderate-intensity aerobic exercise improves children's executive function. 3) ReHo increases in bilateral posterior buckle gyrus, bilateral central parietal posterior gyrus, and left dorsal lateral prefrontal lobe are significantly associated with improved executive function. Conclusions: Short-term moderate-intensity aerobic exercise can improve brain plasticity and executive function by increasing local consistency of brain function in children at rest. Level of evidence II; Therapeutic studies - investigation of treatment results.

RESUMO Introdução: O rápido desenvolvimento dos rs-fMRI nos últimos anos pode fornecer novas evidências científicas da plasticidade do cérebro da criança. Objetivo: revelar o efeito do exercício aeróbio de intensidade moderada de curta duração na consistência local da função cerebral em crianças em repouso e fornecer novas evidências para elucidar a relação entre exercício físico e plasticidade cerebral em crianças. Métodos: Usando a tecnologia de imagem de ressonância magnética funcional em estado de repouso (rs-fMRI) e o método de análise de consistência local (ReHo) para detectar exercícios aeróbicos de intensidade moderada e de curta duração 30 minutos antes e depois de alterações de consistência local na função cerebral das crianças; usando a medição de Flanker das mudanças na função executiva das crianças antes e depois do exercício. Resultados: 1) Um curto exercício aeróbico de 30 min de intensidade moderada fez com que as crianças se curvassem para trás, lobo pré-frontal dorsolateral esquerdo, giro frontal medial esquerdo, giro central posterior bilateral, giro suboccipital esquerdo e giro da língua. 2) Um exercício aeróbico de curta duração, 30 minutos e intensidade moderada melhora a função executiva das crianças. 3) Aumentos em ReHo no giro da fivela posterior bilateral, no giro parietal posterior central bilateral e no lobo pré-frontal lateral dorsal esquerdo estão significativamente associados à função executiva melhorada. Conclusões: O exercício aeróbico de intensidade moderada de curto prazo pode melhorar a plasticidade cerebral e a função executiva, aumentando a consistência local da função cerebral em crianças em repouso. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: El rápido desarrollo de rs-fMRI en los últimos años puede proporcionar nueva evidencia científica de la plasticidad del cerebro del niño. Objetivo: Revelar el efecto del ejercicio aeróbico de intensidad moderada a corto plazo sobre la consistencia local de la función cerebral en niños en reposo y proporcionar nueva evidencia para dilucidar la relación entre el ejercicio físico y la plasticidad del cerebro de los niños. Métodos: uso de la tecnología de imágenes de resonancia magnética funcional (rs-fMRI) en estado de reposo y el método de análisis de consistencia local (ReHo) para detectar un ejercicio aeróbico de intensidad moderada a corto plazo de 30 minutos antes y después de los cambios de consistencia local de la función cerebral de los niños; utilizando la medición de Flanker de los cambios en la función ejecutiva de los niños antes y después del ejercicio. Resultados: 1) Un ejercicio aeróbico de intensidad moderada y corta duración de 30 min hizo que los niños se doblaran hacia atrás, lóbulo prefrontal dorsolateral izquierdo, circunvolución medial frontal izquierda, circunvolución posterior central bilateral, circunvolución suboccipital izquierda y circunvolución de la lengua. 2) Un ejercicio aeróbico de intensidad moderada a corto plazo de 30 minutos mejora la función ejecutiva de los niños. 3) Los aumentos de ReHo en la circunvolución de la hebilla posterior bilateral, la circunvolución posterior parietal central bilateral y el lóbulo prefrontal lateral dorsal izquierdo se asocian significativamente con una función ejecutiva mejorada. Conclusiones: El ejercicio aeróbico de intensidad moderada a corto plazo puede mejorar la plasticidad cerebral y la función ejecutiva al aumentar la consistencia local de la función cerebral en niños en reposo. Nivel de evidencia II; Estudios terapéuticos: investigación de los resultados del tratamiento.

Research progress on hippocampal-avoidance whole brain radiotherapy / 中华放射肿瘤学杂志

With the advancement of imaging diagnosis and the development of modern radiotherapy, the survival of cancer patients has been prolonged and the incidence rate of brain metastases (BM) has been significantly increased. The quality of life of patients and potential radiotherapy-induced neurocognitive impairment have gradually captivated widespread attention. Whole brain radiotherapy (WBRT) is one of the common local therapies for BM patients. However, the application of WBRT is controversial because it may lead to neurocognitive impairment. The incidence of metastatic tumors in hippocampus and radiation-induced neurocognitive impairment can accelerate the implementation of hippocampal-avoidance WBRT (HA-WBRT). In this article, the feasibility of HA-WBRT was discussed and research progress in recent years was reviewed.

Dosimetric study of hippocampal protective whole brain radiotherapy based on Varian accelerator / 中国辐射卫生

Objective The purpose of this study is to provide a reference for the selection of clinical radiotherapy plan by comparing the difference of dosimetry between coplanar dynamic intensity modulation dIMRT and coplanar VMAT plan in hippocampal protective whole brain radiotherapy (WBRT). Methods 10 patients were selected whose hippocampal were protected by WBRT, dIMRT and VMAT plans were designed for each patient, the differences of target dose, organ-endangering dose and machine hop count were compared between the two groups. Results The two technical plans PTV V30 Gy, D98% and D2% all meet the standard of RTOG 0933, which is better than the dIMRT group for the PTV HI VMAT group (P = 0.004). The hippocampal dose of dIMRT group was better than that of VMAT group, but it did not meet the standard of RGOT 0933. The average Dmax of hippocampus in dIMRT group and VMAT group was 18.44 Gy and 19.30 Gy, respectively (P = 0.004). The average value of hippocampal Dmin was 10.03 Gy and 10.77 Gy, respectively (P = 0.013), and the mean value of hippocampal Dmean was 14.20 Gy and 15.12 Gy, respectively (P = 0.002). The doses of lens, eyeball and optic nerve all met the standard of RTOG0933, and the dose of dIMRT group was significantly better than that of VMAT group (P = 0.000). The treatment time in VMAT group was significantly lower than that in dIMRT group. The treatment time in VMAT group was significantly lower than that in dIMRT group. Conclusion Varian dIMRT has more advantages in controlling hippocampal dose and protecting lens than VMAT, but PTV HI and treatment efficiency are higher in VMAT group.

Divergent Projection Patterns Revealed by Reconstruction of Individual Neurons in Orbitofrontal Cortex / 神经科学通报·英文版

The orbitofrontal cortex (OFC) is involved in diverse brain functions via its extensive projections to multiple target regions. There is a growing understanding of the overall outputs of the OFC at the population level, but reports of the projection patterns of individual OFC neurons across different cortical layers remain rare. Here, by combining neuronal sparse and bright labeling with a whole-brain florescence imaging system (fMOST), we obtained an uninterrupted three-dimensional whole-brain dataset and achieved the full morphological reconstruction of 25 OFC pyramidal neurons. We compared the whole-brain projection targets of these individual OFC neurons in different cortical layers as well as in the same cortical layer. We found cortical layer-dependent projections characterized by divergent patterns for information delivery. Our study not only provides a structural basis for understanding the principles of laminar organizations in the OFC, but also provides clues for future functional and behavioral studies on OFC pyramidal neurons.

Successful treatment of nonsmall cell lung cancer patients with leptomeningeal metastases using whole brain radiotherapy and tyrosine kinase inhibitors

The efficacy of treatments in patients with nonsmall cell lung cancer (NSCLC) with leptomeningeal metastases (LMs) remains unclear. Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) play an important role in the treatment of patients with NSCLC. However, few studies have investigated the efficacy of combination therapy with TKIs and whole brain radiotherapy (WBRT) in patients with NSCLC/LM. We report here the case of a male patient in his 60s with adenocarcinoma who underwent lobectomy of the right upper lobe. The cancer was classified as pT1bN1M0 Stage IIA, and a mutational analysis revealed the presence of an EGFR mutation. However, 6 months after standard chemotherapy, LM had developed and WBRT was administered. Gefitinib (250 mg/day) was administered after WBRT. The patient remained free of significant recurrent disease for 57 months after WBRT was administered. Combination therapy with TKIs and WBRT is associated with relatively long survival times in patients with LM

Estimación del tiempo de Sobrevida después de Radioterapia Holoencefálica en Metástasis Cerebrales / Estimation of Survival time after Holoencephalic Radiotherapy in Brain Metastases

Introducción: Las metástasis cerebrales constituyen una causa importante de mortalidad y son los tumores intracraneales más comunes en adultos, ocurren en aproximadamente el 20% y el 40% de los pacientes diagnosticados con cáncer. Los factores pronósticos que permiten estimar la esperanza de vida, son las herramientas que se deberían usar para proponer el fraccionamiento y duración del tratamiento con energía radiante. Métodos: Estudio de tipo retrospectivo realizado en el Hospital de Solón Espinosa Ayala, SOLCA-Quito. Se registraron los pacientes con metástasis cerebrales tratados con radioterapia holoencefálica en el período comprendido entre enero del 2003 a diciembre del 2018. Para el análisis de supervivencia se usaron las curvas de Kaplan Meier y la significación de diferencias con la prueba de Long-rank con un error tipo I o alfa del 5%. Además se realizó un análisis bivariado con el modelo de regresión logística de Cox entre la mediana de supervivencia y las variables: Indice de Karnofsky (IK), edad, número de metástasis cerebrales, metástasis extracraneales, tumor primario y la escala "Graded Prognostic Assessment" (GPA). Resultados: Se registraron309 pacientes, la mediana de supervivencia global fue de 5 meses. Todos los factores afectan la supervivencia (p ≤0.05); los que alcanzaron los mejores resultados en términos de sobrevida fueron: IK ≥90, grupo etario entre 51-60 años, los pacientes con 1 metástasis cerebral, ausencia de metástasis extra craneales y las metástasis cerebrales originadas en mama con puntuaciones de GPA entre 3.5-4. Conclusión: La edad, el índice de Karnofsky, el número de metástasis cerebrales, la presencia de metástasis extra craneales, tumor primario y clasificación GPA son factores que permiten estimar el tiempo de supervivencia en pacientes con metástasis cerebrales

Introduction: Brain metastases are an important cause of mortality and the most common intracranial tumors in adults, observed in approximately 20% and 40% of patients diagnosed with cancer. The prognostic factors that allow estimating life expectancy are the tools that should be used to propose the fractionation and duration of the radiant energy treatment. Methods: The present retrospective study was carried out at the Solón Espinosa Ayala Hospital, SOLCA-Quito. The patients who received whole brain radiotherapy in the study period from January 2003 to December 2018, were registered. For survival analysis, use the Kaplan Meier curves and the significance of differences with the long-range test with a 5% type I or alpha error. In addition, a bivariate analysis was performed with the Cox logistic regression model between the median survival and the variables: Karnofsky index (IK), age, number of brain metastases, extracranial metastases, primary tumor and the "Graded Prognostic Assessment" (GPA). Results: 309 patients were registered and the median overall survival of patients with brain metastases treated with whole brain radiotherapy was 5 months. All factors affect survival (p ≤ 0.05); those who achieved the best results in terms of survival were: Karnofsky Performance Status (KPS) ≥ 90, age group between 51-60 years, patients with 1 brain metastasis, absence of extracranial metastases and brain metastases originated in breasts with Graded Prognostic Assessment (GPA) score between 3.5- 4. Conclusion: Age, KPS, number of brain metastases, presence of extracranial metastases, primary tumor and GPA are factors that allow estimating survival time in patients with brain metastases