Relationship between multi-pool model-based chemical exchange saturation transfer imaging, intravoxel incoherent motion MRI, and 11C-methionine uptake on PET/CT in patients with gliomas.

PURPOSE: Magnetization transfer ratio asymmetry (MTRasym) analysis is used for chemical exchange saturation transfer (CEST) in patients with gliomas; however, this approach has limitations. CEST imaging using a multi-pool model (MPM) may allow a more detailed assessment of gliomas; however, its mechanism remains unknown. This study aimed to assess the relationship between CEST imaging by MPM, intravoxel incoherent motion (IVIM), and 11C-methionine (11C-MET) uptake on positron emission tomography/computed tomography (PET/CT) to clarify the clinical significance of CEST imaging using MPM in gliomas. METHODS: This retrospective study included 17 patients with gliomas who underwent 11C-MET PET/CT at our institution between January 2020 and January 2022. Two-dimensional axial CEST imaging was conducted using single-shot fast-spin echo acquisition at 3 T. The apparent diffusion coefficient (ADC), true diffusion coefficient (D), pseudo-diffusion coefficient (D*), f, MTRasym (3.5 ppm), parameters of MPM-based CEST imaging, and tumor-to-contralateral normal brain tissue (T/N) ratio were calculated using a region-of-interest analysis. Shapiro-Wilk test, weighted kappa coefficient, and Spearman's rank correlation coefficients were used for statistical analysis. RESULTS: Significant correlations were found between APT_T1 and T/N ratio (ρ = 0.87, p < 0.001), APT_T2 and T/N ratio (ρ = 0.47, p < 0.05), MTRasym and T/N ratio (ρ = 0.55, p < 0.01), and T2/T1 and T/N ratio (ρ = -0.36, p < 0.05). Furthermore, significant correlations were observed between APT_T1 and ADC (ρ = -0.67, p < 0.001), APT_T1 and D (ρ = -0.70, p < 0.001), APT_T2 and D* (ρ = -0.45, p < 0.05), and T2/T1 and D (ρ = 0.39, p < 0.05). CONCLUSION: These preliminary findings indicate that MPM-based CEST imaging parameters correlate with IVIM and 11C-MET uptake on PET/CT in patients with gliomas. In particular, the new parameter APT_T1 correlated more strongly with 11C-MET uptake compared to the traditional CEST parameter MTRasym.

Status of alternative angiogenic pathways in glioblastoma resected under and after bevacizumab treatment.

Glioblastoma multiforme (GBM) acquires resistance to bevacizumab (Bev) treatment. Bev affects angiogenic factors other than vascular endothelial growth factor (VEGF), which are poorly understood. We investigated changes in angiogenic factors under and after Bev therapy, including angiopoietin-1 (ANGPT1), angiopoietin-2 (ANGPT2), placental growth factor (PLGF), fibroblast growth factor 2, and ephrin A2 (EphA2). Fifty-four GBM tissues, including 28 specimens from 14 cases as paired specimens from the same patient obtained in three settings: initial tumor resection (naïve Bev), tumors resected following Bev therapy (effective Bev), and recurrent tumors after Bev therapy (refractory Bev). Immunohistochemistry assessed their expressions in tumor vessels and its correlation with recurrent MRI patterns. PLGF expression was higher in the effective Bev group than in the naïve Bev group (p = 0.024) and remained high in the refractory Bev group. ANGPT2 and EphA2 expressions were higher in the refractory Bev group than in the naïve Bev group (p = 0.047 and 0.028, respectively). PLGF expression was higher in the refractory Bev group compared with the naïve Bev group for paired specimens (p = 0.036). PLGF was more abundant in T2 diffuse/circumscribe patterns (p = 0.046). This is the first study to evaluate angiogenic factors other than VEGF during effective and refractory Bev therapy in patient-derived specimens.

A Case of Idiopathic Peptic Ulcer Disease Treated Effectively with Trimebutine Maleat.

A 30-year-old man with idiopathic peptic ulcer disease (IPUD) experienced repeated recurrence of ulcerative bleeding despite treatment with lansoprazole and then vonoprazan. Further evaluation suggested that the cause of the ulcer was strong contractile movements of the antrum. This prompted the co-administration of trimebutine maleate (TM) and vonoprazan to relieve the stomach contractions. TM was effective in preventing the recurrence of ulcerative bleeding, and the patient has remained in remission for 4 years. This case highlights the potential efficacy of TM in treating IPUD and the importance of considering hypercontractility as the underlying cause in cases of IPUD.

An exploratory prospective phase II study of preoperative neoadjuvant bevacizumab and temozolomide for newly diagnosed glioblastoma.

PURPOSE: This multi-institutional phase I/II study was conducted to confirm the safety and explore the clinical utility of preoperative Bevacizumab (Bev) for newly diagnosed glioblastoma (GB). METHODS: Patients were enrolled based on magnetic resonance imaging (MRI) findings typically suggestive of GB. Preoperative Bev and temozolomide (TMZ) were administered at doses of 10 mg/kg on day 0 and 150 mg/m2 on days 1-5, respectively. Surgical resection was performed between days 21 and 30, inclusive. The safety and efficacy were evaluated in a total of 15 cases by progression-free survival (PFS), changes in tumor volume, Karnofsky Performance Scale (KPS) and Mini-Mental State Examination (MMSE) scores after preoperative therapy. RESULTS: Tumor resection was performed on a mean of day 23.7. Pathological diagnosis was GB, isocitrate dehydrogenase (IDH)-wildtype in 14 cases and GB, IDH-mutant in 1 case. Severe adverse events possibly related to preoperative Bev and TMZ were observed in 2 of the 15 patients, as wound infection and postoperative hematoma and thrombocytopenia. KPS and MMSE scores were significantly improved with preoperative therapy. Tumor volume was decreased in all but one case on T1-weighted imaging with contrast-enhancement (T1CE) and in all cases on fluid-attenuated inversion recovery, with mean volume decrease rates of 36.2% and 54.0%, respectively. Median PFS and overall survival were 9.5 months and 16.5 months, respectively. CONCLUSION: Preoperative Bev and TMZ is safe as long as the instructions are followed. The strategy might be useful for GB in some patients, not only reducing tumor burden, but also improving patient KPS preoperatively. TRIAL REGISTRATION NUMBER: UMIN000025579, jRCT1031180233 https://jrct.niph.go.jp/latest-detail/jRCT1031180233 . Registration Date: Jan. 16, 2017.

Comparative evaluation of 11C-methionine and 18F-fluorodeoxyglucose positron emission tomography for distinguishing between primary central nervous system lymphoma and isocitrate dehydrogenase-wildtype glioblastoma.

PURPOSE: Distinguishing between primary central nervous system lymphoma (PCNSL) and isocitrate dehydrogenase (IDH)-wildtype glioblastoma is important for therapeutic decision-making. This study aimed to compare the performance of 11C-methionine (MET) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) for distinguishing between these two major malignant brain tumors. METHODS: We retrospectively conducted qualitative and semiquantitative analyses of pre-treatment MET and FDG PET/computed tomography (CT) images of 22 patients with PCNSL and 64 patients with IDH-wildtype glioblastoma. For semiquantitative analysis, we calculated the tumor-to-normal tissue (T/N) ratio by dividing the maximum standardized uptake value (SUV) for the tumor (T) by the average SUV for the normal tissue (N). For performance evaluation, we employed receiver operating characteristic curve analysis and calculated the areas under the curve (AUC) values. RESULTS: In the qualitative analysis, all PCNSLs and IDH-wildtype glioblastomas were MET-positive, while 95% and 84% of PCNSLs and IDH-wildtype glioblastomas, respectively, were FDG-positive. Eleven patients were excluded from the FDG PET/CT semiquantitative analysis because of hyperglycemia. There was no difference in MET T/N ratio between PCNSL and IDH-wildtype glioblastoma (p = 0.37). FDG T/N ratio was significantly higher in PCNSL than in IDH-wildtype glioblastoma (p < 0.001). The AUC value for distinguishing PCNSL from IDH-wildtype glioblastoma was significantly higher for the FDG T/N ratio (0.871) than for the MET T/N ratio (0.565) (p = 0.0027). CONCLUSION: MET PET could detect both PCNSL and IDH-wildtype glioblastoma, but unlike FDG PET, it could not distinguish between these two major malignant brain tumors.

Antiproliferative effects of D-allose associated with reduced cell division frequency in glioblastoma.

Recent studies have shown that D-allose, a rare sugar, elicits antitumor effects on different types of solid cancers, such as hepatocellular carcinoma, non-small-cell lung cancer, and squamous cell carcinoma of the head and neck. In this study, we examined the effects of D-allose on the proliferation of human glioblastoma (GBM) cell lines (i.e., U251MG and U87MG) in vitro and in vivo and the underlying mechanisms. D-allose treatment inhibited the proliferation of U251MG and U87MG cells in a dose-dependent manner (3-50 mM). However, D-allose treatment did not affect cell cycles or apoptosis in these cells but significantly decreased the cell division frequency in both GBM cell lines. In a subcutaneous U87MG cell xenograft model, intraperitoneal injection of D-allose (100 mg/kg/day) significantly reduced the tumor volume in 28 days. These data indicate that D-allose-induced reduction in cell proliferation is associated with a subsequent decrease in the number of cell divisions, independent of cell-cycle arrest and apoptosis. Thus, D-allose could be an attractive additive to therapeutic strategies for GBM.

A Prospective Study of Intensity-modulated Radiation Therapy Using a Standard Radiation Dose for High-grade Glioma.

BACKGROUND/AIM: We evaluated the treatment outcomes of intensity-modulated radiation therapy (IMRT) using a standard radiation dose in patients with high-grade glioma (HGG). PATIENTS AND METHODS: We conducted a prospective, single-institutional, single-arm trial. Patients aged 20-75 years with histologically proven HGG were enrolled. Surgical procedures and chemotherapy regimens were not regulated. The prescribed dose of postoperative IMRT was 60 Gy in 30 fractions over six weeks. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS), completion rate of IMRT, and Grade 3 or higher non-hematological toxicity. RESULTS: Between 2016 and 2019, 20 patients were enrolled. According to the World Health Organization 2016 Classification, glioblastoma, anaplastic astrocytoma, and anaplastic oligodendroglioma were present in nine, six, and five of the recruited patients, respectively. Gross total resection, partial resection, and biopsy were performed in four, nine, and seven patients, respectively. All patients received concurrent and adjuvant chemotherapy using temozolomide with or without bevacizumab. The completion rate of IMRT was 100%. The median follow-up period was 29 months (range=6-68 months). Median OS and PFS were 30 and 14 months, respectively. No patients experienced Grade 3 or higher non-hematological toxicity. The 2-year OS rates were 100%, 57%, and 33% in Radiation Therapy Oncology Group-Recursive Partitioning Analysis (RTOG-RPA) classes I/II, IV, and V, respectively (p=0.002; log-rank test). CONCLUSION: IMRT using the standard radiation dose in patients with HGG can be carried out safely. RTOG-RPA class appears to be useful to estimate patient prognoses.

18F-Fluoromisonidazole-Positron Emission Tomography and Immunohistochemistry Verified Tumor Oxygenation, Stemness, and Immunosupportive Microenvironment After Preoperative Neoadjuvant Bevacizumab for Newly Diagnosed Glioblastoma.

BACKGROUND: Cancer stemness and immunosuppressive tumor microenvironment (TME) in accordance with tumor oxygenation are variable during bevacizumab (Bev) therapy for glioblastoma (GBM). Positron emission tomography (PET) using 18F-fluoromisonidazole (FMISO) reflects hypoxic TME. The aim of this study was to compare FMISO-PET and immunohistochemical findings of tumor oxygenation in the TME of GBM during Bev treatment. METHODS: Seven patients with newly diagnosed IDH-wildtype GBM underwent FMISO-PET during follow-up. Three patients received preoperative neoadjuvant Bev (neo-Bev) and subsequently underwent surgical resection. Reoperation was performed at the recurrence. FMISO-PET was performed before and after neo-Bev. Four patients who underwent tumor resection without neo-Bev were included as the control group. Expressions of hypoxic markers (carbonic anhydrase; CA9), stem cell markers (nestin, FOXM1), and immunoregulatory molecules (CD163, FOXP3, PD-L1) in tumor tissues were analyzed by immunohistochemistry (IHC). RESULTS: All 3 patients treated with neo-Bev showed decrease in FMISO accumulation in accordance with expressions of CA9 and FOXM1 compared with the control group. Two of these 3 patients at the recurrence showed increase in FMISO accumulation. IHC showed increased CA9-and FOXM1-positive cells in recurrent tumors. Expression of PD-L1 tended to be lower after neo-Bev compared with the control group. CONCLUSIONS: FMISO-PET effectively visualized TME oxygenation after neo-Bev. Increased FMISO accumulation at the time of recurrence, even under Bev treatment, suggests that FMISO-PET might be useful for monitoring the duration of Bev efficacy by reflecting tumor oxygenation.

Effects of a monoclonal antibody against (pro)renin receptor on gliomagenesis.

Glioblastoma is characterized by a strong self-renewal potential and poor differentiated state. We have reported previously that the (pro)renin receptor [(P)RR] is a potential target for glioma therapy by silencing the (P)RR gene. Here, we have examined the effects of a monoclonal antibody against (P)RR on gliomagenesis. Human glioma cell lines (U251MG and U87MG) and a glioma stem cell line (MGG23) were used for the in vitro study. The expressions of the Wnt/ß-catenin signaling pathway (Wnt signaling pathway) components and stemness markers were measured by Western blotting. The effects of the (P)RR antibody on cell proliferation, sphere formation, apoptosis and migration were also examined. Subcutaneous xenografts were also examined in nude mice. Treatment with the (P)RR antibody reduced expression of Wnt signaling pathway components and stemness markers. Furthermore, the (P)RR antibody reduced cell proliferation and decreased sphere formation significantly. The treatment also suppressed migration and induced apoptosis. In a subcutaneous xenograft model, systemic administration of the (P)RR antibody reduced tumor volume significantly. These data show that treatment with the (P)RR antibody is a potential therapeutic strategy for treating glioblastoma.

d-Allulose Supplementation Prevents Diet-Induced Hepatic Lipid Accumulation via miR-130-Mediated Regulation in C57BL/6 Mice.

SCOPE: d-allulose is a low-calorie rare sugar. It has been reported that d-allulose supplementation significantly inhibits diet-induced hepatic fat accumulation. However, the underlying molecular mechanisms remain unclear. This study elucidates the mechanism underlying the suppressive effect of d-allulose on hepatic fat accumulation in terms of miRNA regulation. METHODS AND RESULTS: Male C57BL/6 mice are divided into three experimental groups-normal diet and distilled water (CC group), high-fat diet (HFD) and distilled water (HC group), and HFD and 5% d-allulose solution (HA group)-and fed the respective diets for 8 weeks. Weight gain is significantly lower in the HA group than that in the HC group, although the caloric intake is the same in both. Histological analysis of liver tissues reveals excessive lipid accumulation in the HC group; this is greatly attenuated in the HA group. Real-time PCR and western blot analyses demonstrate that, compared to the HC group, the HA group exhibits decreased hepatic PPARγ and CD36 expression. Hepatic miR-130 expression levels are higher in the HA group than those in the CC and HC groups. CONCLUSIONS: These results indicate that miRNA changes associated with PPARγ may underlie the suppression of hepatic lipid accumulation induced by d-allulose intake.

Regenerative Effect of Umbilical Cord-Derived Mesenchymal Stromal Cells in a Rat Model of Established Limb Ischemia.

BACKGROUND: Although regenerative cell therapy is expected to be an alternative treatment for peripheral artery disease (PAD), many regenerative cell therapies have failed to show sufficient efficacy in clinical trials. Most preclinical studies have used acute ischemia models, despite PAD being a chronic disease. In addition, aging and atherosclerosis decrease the quality of a patient's stem cells. Therefore, using a non-acute ischemic preclinical model and stem cells with high regenerative potency are important for the development of effective regenerative therapy. In this study, we assessed the tissue regenerative potential of umbilical cord-derived mesenchymal stromal cells (UCMSCs), which could potentially be an ideal cell source, in a rat model of established ischemia.Methods and Results: The regenerative capacity of UCMSCs was analyzed in terms of angiogenesis and muscle regeneration. In vitro analysis showed that UCMSCs secrete high amounts of cytokines associated with angiogenesis and muscle regeneration. In vivo experiments in a rat non-acute ischemia model showed significant improvement in blood perfusion after intravenous injection of UCMSCs compared with injection of culture medium or saline. Histological analysis revealed UCMSCs injection enhanced angiogenesis, with an increased number of von Willebrand factor-positive microcapillaries, and improved muscle regeneration. CONCLUSIONS: These results suggest that intravenous administration of UCMSCs may be useful for treating patients with PAD.

Perioperative Clinical Course Variables Associated with Length of Hospital Stay after Primary Intracranial Meningioma Resection.

The relationship between perioperative clinical course variables and postoperative length of hospital stay (LOS) in patients undergoing primary intracranial meningioma resection has not been fully elucidated. We therefore aimed to identify the perioperative clinical course variables that predict postoperative LOS in such patients. We retrospectively collected data concerning demographics, tumor characteristics, and perioperative clinical course variables in 76 patients who underwent primary intracranial meningioma resection between January 2010 and December 2019, and tested for associations with postoperative LOS. Univariate analyses showed that younger age, fewer days to postoperative initiation of standing/walking, preoperative independence in activities of daily living (ADL), and ADL independence one week after surgery were associated with shorter postoperative LOS. Multiple regression analyses with these factors identified that days to stand/walk initiation and ADL independence one week after surgery were associated with postoperative LOS. Based on these results, we conclude that rehabilitation programs that promote early mobilization and the early acquisition of independence may reduce postoperative LOS in patients who undergo primary intracranial meningioma resection.

Engineered clustered myoblast cell injection augments angiogenesis and muscle regeneration in peripheral artery disease.

The low survival rate of administered cells due to ischemic and inflammatory environments limits the efficacy of the current regenerative cell therapy in peripheral artery disease (PAD). This study aimed to develop a new method to enhance the efficacy of cell therapy in PAD using cell sheet technology. Clustered cells (CCs) from myoblast cell sheets obtained from C57/BL6 mice were administered into ischemic mouse muscles 7 days after induction of ischemia (defined as day 0). Control groups were administered with single myoblast cells (SCs) or saline. Cell survival, blood perfusion of the limb, angiogenesis, muscle regeneration, and inflammation status were evaluated. The survival of administered cells was markedly improved in CCs compared with SCs at days 7 and 28. CCs showed significantly improved blood perfusion, augmented angiogenesis with increased density of CD31+/α-smooth muscle actin+ arterioles, and accelerated muscle regeneration, along with the upregulation of associated genes. Additionally, inflammation status was well regulated by CCs administration. CCs administration increased the number of macrophages and then induced polarization into an anti-inflammatory phenotype (CD11c-/CD206+), along with the increased expression of genes associated with anti-inflammatory cytokines. Our findings suggest clinical potential of rescuing severely damaged limbs in PAD using CCs.

Endovascular Treatment for Posterior Communicating Artery Aneurysms with Oculomotor Nerve Palsy.

Objective: Coil embolization for the treatment of internal carotid artery-posterior communicating artery aneurysms (PComAAn) associated with oculomotor nerve palsy (ONP) remains controversial in terms of the therapeutic effect to improve ONP. Patients with PComAAn treated in our hospital were retrospectively analyzed to evaluate the effectiveness of coil embolization on ONP. Methods: Twenty-three patients who had coil embolization for PComAAn with ONP were included in the analysis. In the evaluation of postoperative outcome of ONP, complete resolution of all symptoms was considered as a total recovery. ONP with a few residual symptoms that are stable and not disabling was considered as a subtotal recovery and that with only a slight improvement as a partial recovery. Results: Preoperative ONP was complete palsy in 14 and partial palsy in nine cases. The mean maximum diameter of the aneurysms was 9.1 ± 3.5 mm (3-17 mm), and the mean time from the onset to treatment was 46.3 ± 98.4 days (0-300 days). The embolization state immediately after the procedure was complete occlusion in seven, neck remnant in eight, and body filling (BF) in eight cases. Total recovery was observed in nine, subtotal recovery in 11, and partial recovery in three cases. The mean time to any improvement in ONP was 6.0 ± 6.0 months (0.5-25 months). Comparing 20 cases with total plus subtotal recovery and three cases with partial recovery, five (25.0%) and three (100%) cases showed BF immediately after the procedure, respectively, which was statistically significant (P = 0.015). Conclusion: The analysis indicated that coil embolization for the treatment of PComAAn with ONP resulted in satisfactory recovery of ONP in 87% of the cases and the outcome of aneurysm embolization was related to improvement in ONP.

Case Series of Endovascular Therapy for Blood Blister-Like Aneurysm in Acute Phase.

Objective: Blood blister-like aneurysms (BBAs) of the internal carotid artery are highly challenging to treat due to their variable morphology and tendency for rupture and regrowth. Here, we report a single-institution experience of endovascular therapy (EVT) for BBA treatment. Methods: We retrospectively reviewed patients with ruptured BBA from 2006 to 2019. All patients in whom BBA was treated with EVT were included. Patients' aneurysmal characteristics, progression status, aneurysm occlusion on follow-up angiography, and modified Rankin Scale (mRS) score were recorded. Results: A total of 11 patients (5 women and 6 men) with the mean age of 46 ± 10 years were included in this study. As initial treatment, 9 patients were treated with stent-assisted coiling (SAC). Immediate angiographic results showed that 2 cases were body filling, 4 were neck remnant, and 3 were complete obliteration. Perioperative ischemic complications were not observed. On postoperative day 1, 2 patients suffered from rerupture, and their prognoses were poor. Retreatments were performed in 5 patients. Parent artery occlusion (PAO) was performed in 6 patients including 2 initial treatments and 4 retreatments. Symptomatic infarction developed in 2 patients. In 3 patients, bypass in combination with PAO was performed. Clinical data revealed discharge mRS scores of 0-2 and 3-6 in 4 and 7 patients, respectively. Conclusion: SAC is effective for the management of BBA. Careful follow-up and response are necessary after treatment with SAC.

Distinguishing between primary central nervous system lymphoma and glioblastoma using [18F]fluoromisonidazole and [18F]FDG PET.

OBJECTIVE: The purpose of this study was to assess the diagnostic value of [18F]fluoromisonidazole (FMISO) and 2-deoxy-2-[18F]fluoro-D-glucose (FDG) PET to discriminate primary central nervous system lymphoma (PCNSL) from glioblastoma. METHODS: FMISO and FDG PET/CT scans before therapy obtained in 13 patients with PCNSL and in 62 patients with glioblastoma were retrospectively reviewed. PET results were evaluated by visual and semiquantitative analysis. For semiquantitative analysis, the maximum standardized uptake value (SUV) for tumor (T) and the mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. The performance in discriminating PCNSL and glioblastoma was evaluated using a receiver-operating characteristics analysis. Area-under-the-curve (AUC) values for the discrimination were calculated. RESULTS: On visual analysis, 54% of PCNSL and 89% of glioblastoma showed positive on FMISO PET. All patients with PCNSL and glioblastoma were FDG positive. FMISO T/N ratio in PCNSL (mean ± SD = 1.80 ± 0.59) was significantly lower than that in glioblastoma (mean ± SD = 2.75 ± 0.84) (P < 0.001). FDG T/N ratio in PCNSL (mean ± SD = 3.01 ± 1.11) was significantly higher than that in glioblastoma (mean ± SD = 1.77 ± 0.79) (P < 0.001). For discrimination of patients with PCNSL from glioblastoma, the AUC values for the FMISO T/N ratio, FDG T/N ratio and combination of the two parameters were 0.833, 0.825 and 0.900, respectively. CONCLUSION: FMISO PET is as helpful for differentiating PCNSL from glioblastoma as FDG PET.

Temporal and spatial changes in reactive astrogliosis examined by 18F-THK5351 positron emission tomography in a patient with severe traumatic brain injury.

BACKGROUND: The positron emission tomography (PET) radioligand 18F-THK5351 is now used to evaluate monoamine oxidase B expression in the reactive astrogliosis seen in various central nervous diseases. Traumatic brain injury (TBI) is known to induce reactive astrogliosis in the lesion site. This is a first report to examine the spatial and temporal changes in reactive astrogliosis as evaluated by 18F-THK5351 after a severe TBI. CASE PRESENTATION: A 27-year-old man suffering from a severe TBI with multiple brain contusions was examined using 18F-THK5351 PET/CT in the subacute and chronic phases after the injury. The first PET scan, performed 46 days after the TBI, showed intense uptake of 18F-THK5351 in and around the brain contusions. The second PET scan, performed 271 days after the TBI, showed reduced uptake of 18F-THK5351 at the original sites of the brain contusions and increased uptakes in the white matter surrounding the contusions and the corpus callosum. The patient exhibited sustained improvement of neuropsychological impairment between the two PET examinations and remarkable recovery from the severe TBI. CONCLUSIONS: There were evident temporal and spatial changes in 18F-THK5351 uptake in the traumatized brain between the two PET examinations. These changes may have been related to the remarkable neurological recovery in this patient. The degree and distribution of reactive astrogliosis detected by 18F-THK5351 PET may be useful in assessing pathophysiology and predicting prognosis in TBI patients.

Fractal analysis of 11C-methionine PET in patients with newly diagnosed glioma.

BACKGROUND: The present study tested the possible utility of fractal analysis from L-[methyl-11C]-methionine (MET) uptake in patients with newly diagnosed gliomas for differentiating glioma, especially in relation to isocitrate dehydrogenase 1 (IDH1) mutation status, and as compared with the conventional standardized uptake value (SUV) parameters. METHODS: Investigations of MET PET/CT were performed retrospectively in 47 patients with newly diagnosed glioma. Tumors were divided into three groups: lower grade glioma (IDH1-mutant diffuse astrocytoma and IDH1-mutant anaplastic astrocytoma), higher grade glioma (IDH1-wildtype diffuse astrocytoma and IDH1-wildtype anaplastic astrocytoma), and glioblastoma. The fractal dimension for tumor, maximum SUV (SUVmax) for tumor (T) and mean SUV for normal contralateral hemisphere (N) were calculated, and the tumor-to-normal (T/N) ratio was determined. Metabolic tumor volume (MTV) and total lesion MET uptake (TLMU) were also measured. RESULTS: There were significant differences in SUVmax (p = 0.006) and T/N ratio (p = 0.02) between lower grade glioma and glioblastoma. There were no significant differences among any of the three groups in MTV or TLMU. Significant differences were obtained in the fractal dimension between lower grade glioma and higher grade glioma (p = 0.006) and glioblastoma (p < 0.001). CONCLUSIONS: The results of this preliminary study in a small patient population suggest that the fractal dimension using MET PET in patients with newly diagnosed gliomas is useful for differentiating glioma, especially in relation to IDH1 mutation status, which has not been possible with SUV parameters.

[Points to Note about Neuropsychological Impairment in the Acute Management of Traumatic Brain Injury].

Neuropsychological impairment after traumatic brain injury(TBI)is occasionally difficult to diagnose and called "invisible or hidden impairment," especially when physical impairment is mild. Patients and their family do not recognize the impairment during hospitalization and even after discharge. However, they manifest many problems when they return to real life and society. Here, we have presented the characteristics and tips to diagnose neuropsychological impairment after TBI that are important for clinical neurosurgeons working at acute care hospitals. They are as follows: 1)In the emergency room, accurate evaluation of the consciousness state is the first step. 2)In the acute phase after TBI, do not mix up acute symptomatic seizure and post-traumatic epilepsy. 3)Soon after stabilization of the general condition, detailed radiological examinations should be performed to detect organic brain damages with MRI including DWI, FLAIR, T2*, and SWI. 4)At discharge, it is necessary to provide information about neuropsychological impairment to the patients and their family members. Neurosurgeons should diagnose and treat the patients with accurate understanding of neuropsychological impairment in the acute management of TBI.