Fairer AI in ophthalmology via implicit fairness learning for mitigating sexism and ageism.

The transformative role of artificial intelligence (AI) in various fields highlights the need for it to be both accurate and fair. Biased medical AI systems pose significant potential risks to achieving fair and equitable healthcare. Here, we show an implicit fairness learning approach to build a fairer ophthalmology AI (called FairerOPTH) that mitigates sex (biological attribute) and age biases in AI diagnosis of eye diseases. Specifically, FairerOPTH incorporates the causal relationship between fundus features and eye diseases, which is relatively independent of sensitive attributes such as race, sex, and age. We demonstrate on a large and diverse collected dataset that FairerOPTH significantly outperforms several state-of-the-art approaches in terms of diagnostic accuracy and fairness for 38 eye diseases in ultra-widefield imaging and 16 eye diseases in narrow-angle imaging. This work demonstrates the significant potential of implicit fairness learning in promoting equitable treatment for patients regardless of their sex or age.

LncRNAs as nodes for the cross-talk between autophagy and Wnt signaling in pancreatic cancer drug resistance.

Pancreatic cancer is a malignancy with high mortality. In addition to the few symptoms until the disease reaches an advanced stage, the high fatality rate is attributed to its rapid development, drug resistance and lack of appropriate treatment. In the selection and research of therapeutic drugs, gemcitabine is the first-line drug for pancreatic cancer. Solving the problem of gemcitabine resistance in pancreatic cancer will contribute to the progress of pancreatic cancer treatment. Long non coding RNAs (lncRNAs), which are RNA transcripts longer than 200 nucleotides, play vital roles in cellular physiological metabolic activities. Currently, our group and others have found that some lncRNAs are aberrantly expressed in pancreatic cancer cells, which can regulate the process of cancer through autophagy and Wnt/ß-catenin pathways simultaneously and affect the sensitivity of cancer cells to therapeutic drugs. This review presents an overview of the recent evidence concerning the node of lncRNA for the cross-talk between autophagy and Wnt/ß-catenin signaling in pancreatic cancer, together with the practicability of lncRNAs and the core regulatory factors as targets in therapeutic resistance.

Predicting glioblastoma recurrence using multiparametric MR imaging of non-enhancing peritumoral regions at baseline.

Background: To assess the feasibility of multiparametric magnetic resonance imaging in predicting tumor recurrence in nonenhancing peritumoral regions in patients with glioblastoma at baseline. Methods: Fifty-eight patients with recurrent glioblastoma underwent multiparametric magnetic resonance imaging, including T2-weighted fluid-attenuated inversion recovery, diffusion-weighted imaging, and dynamic susceptibility contrast perfusion-weighted imaging. Nonenhancing peritumoral regions with glioblastoma recurrence were identified by coregistering preoperative and post-recurrent magnetic resonance images. Regions of interest were placed in nonenhancing peritumoral regions with and without tumor recurrence to calculate the apparent diffusion coefficient value, and relative ratios of T2-weighted fluid-attenuated inversion recovery signal intensity, apparent diffusion coefficient, and cerebral blood volume values. Results: Significant lower relative T2-weighted fluid-attenuated inversion recovery signal intensity, apparent diffusion coefficient, and relative apparent diffusion coefficient but higher relative cerebral blood volume values were found in the nonenhancing peritumoral regions with tumor recurrence than without recurrence (all P < 0.05). The threshold values ≥ 0.89 for relative cerebral blood volume provide the optimal performance for predicting the nonenhancing peritumoral regions with future tumor recurrence, with the sensitivity, specificity, and accuracy of 84.7%, 83.6%, and 85.8%, respectively. The combination of relative T2-weighted fluid-attenuated inversion recovery signal intensity, apparent diffusion coefficient, and relative cerebral blood volume can provide better predictive performance than relative cerebral blood volume (P = 0.015). Conclusion: The combined use of T2-weighted fluid-attenuated inversion recovery, diffusion-weighted imaging, and dynamic susceptibility contrast perfusion-weighted imaging can effectively estimate the risk of future tumor recurrence at baseline.

The TRPV6 Calcium Channel and Its Relationship with Cancer.

Transient receptor potential vanilloid-6 (TRPV6) is a cation channel belonging to the TRP superfamily, specifically the vanilloid subfamily, and is the sixth member of this subfamily. Its presence in the body is primarily limited to the skin, ovaries, kidney, testes, and digestive tract epithelium. The body maintains calcium homeostasis using the TRPV6 channel, which has a greater calcium selectivity than the other TRP channels. Several pieces of evidence suggest that it is upregulated in the advanced stages of thyroid, ovarian, breast, colon, and prostate cancers. The function of TRPV6 in regulating calcium signaling in cancer will be covered in this review, along with its potential applications as a cancer treatment target.

Sense and anti-sense: Role of FAM83A and FAM83A-AS1 in Wnt, EGFR, PI3K, EMT pathways and tumor progression.

An increasing number of studies have shown that FAM83A, a member of the family with sequence similarity 83 (FAM83), which consists of eight members, is a key tumor therapeutic target involved in multiple signaling pathways. It has been reported that FAM83A plays essential roles in the regulation of Wnt/ß-catenin, EGFR, MAPK, EMT, and other signaling pathways and physiological processes in models of pancreatic cancer, lung cancer, breast cancer, and other malignant tumors. Moreover, the expression of FAM83A could be significantly affected by multiple noncoding RNAs that are dysregulated in malignant tumors, the dysregulation of which is essential for the malignant process. Among these noncoding RNAs, the most noteworthy is the antisense long noncoding (Lnc) RNA of FAM83A itself (FAM83A-AS1), indicating an outstanding synergistic carcinogenic effect between FAM83A and FAM83A-AS1. In the present study, the specific mechanisms by which FAM83A and FAM83A-AS1 cofunction in the Wnt/ß-catenin and EGFR signaling pathways were reviewed in detail, which will guide subsequent research. We also described the applications of FAM83A and FAM83A-AS1 in tumor therapy and provided a certain theoretical basis for subsequent drug target development and combination therapy strategies.

Insights into the Roles of Epigenetic Modifications in Ferroptosis.

Ferroptosis is a non-apoptotic mode of cell death driven by membrane lipid peroxidation and is characterized by elevated intracellular levels of Fe2+, ROS, and lipid peroxidation. Studies have shown that ferroptosis is related to the development of multiple diseases, such as cancer, neurodegenerative diseases, and acute myeloid leukemia. Ferroptosis plays a dual role in the occurrence and development of these diseases. Ferroptosis mainly involves iron metabolism, ROS, and lipid metabolism. Various mechanisms, including epigenetic regulation, have been reported to be deeply involved in ferroptosis. Abnormal epigenetic modifications have been reported to promote tumor onset or other diseases and resistance to chemotherapy drugs. In recent years, diversified studies have shown that epigenetic modification is involved in ferroptosis. In this review, we reviewed the current resistance system of ferroptosis and the research progress of epigenetic modification, such as DNA methylation, RNA methylation, non-coding RNAs, and histone modification in cancer and other diseases by regulating ferroptosis.

ILKAP Promotes the Metastasis of Hepatocellular Carcinoma Cells by Inhibiting ß-Catenin Degradation and Enhancing the WNT Signaling Pathway.

The incidence of Hepatocellular carcinoma (HCC) and HCC-related deaths have remarkably increased over the recent decades. It has been reported that ß-catenin activation can be frequently observed in HCC cases. This study identified the integrin-linked kinase-associated phosphatase (ILKAP) as a novel ß-catenin-interacting protein. ILKAP is localized both in the nucleus and cytoplasm and regulates the WNT pathway in different ways. First, it is demonstrated that ILKAP activates the WNT pathway in HCC cells by increasing the protein level of ß-catenin and other proteins associated with the WNT signaling, such as c-Myc and CyclinD1. Next, it is shown that ILKAP promotes the metastasis of HCC both in vitro and in vivo in a zebrafish xenograft model. It is also found that ILKAP dephosphorylates the GSK3ß and CK1, contributing to the reduced ubiquitination of ß-catenin. Furthermore, it is identified that ILKAP functions by mediating binding between TCF4 and ß-catenin to enhance expression of WNT target genes. Taken together, the study demonstrates a critical function of ILKAP in metastasis of HCC, since ILKAP is crucial for the activation of the WNT pathway via stabilization of ß-catenin and increased binding between TCF4 and ß-catenin.

18F-FDG-PET/CT for Localizing the Epileptogenic Focus in Patients with Different Types of Focal Cortical Dysplasia.

Purpose: To determine the diagnostic and localization value of 18F-fluorodeoxyglucose-positron emission tomography (PET)/computed tomography (CT) in patients with focal cortical dysplasia (FCD) who underwent epilepsy surgery. Methods: One hundred and eight patients with pathologically proven FCD who underwent surgery for refractory epilepsy were retrospectively analyzed. All patients underwent magnetic resonance imaging (MRI), 18F-FDG-PET/CT, and video electroencephalography. An MRI diagnosis of FCD was defined as MRI+. A PET/CT diagnosis of FCD was defined as PET/CT+. Results: MRI and PET/CT detected FCD in 20.37% and 93.52% of patients, respectively. The difference was significant. Twenty-one patients were MRI+/PET+, 80 were MRI-/PET+, six were MRI-/PET-, and one was MRI+/PET-. The MRI positivity rate was lowest in patients with FCD type IIIa (5.6%, P < 0.05). Prevalence of MRI-/PET+ was highest in patients with FCD type IIIa (88.89%, P < 0.05). Conclusion: PET/CT is superior to MRI in detecting FCD. FCD type IIIa was more likely than other types to show MRI-/PET+. This suggests that PET/CT has particular diagnostic value for FCD type IIIa patients with negative MRI findings.

MRI characteristics predict BRAF V600E status in gangliogliomas and pleomorphic xanthoastrocytomas and provide survival prognostication.

BACKGROUND: BRAF V600E mutation is a common genomic alteration in gangliogliomas (GGs) and pleomorphic xanthoastrocytomas (PXAs) with prognostic and therapeutic implications. PURPOSE: To investigate the ability of magnetic resonance imaging (MRI) features to predict BRAF V600E status in GGs and PXAs and their prognostic values. MATERIAL AND METHODS: A cohort of 44 patients with histologically confirmed GGs and PXAs was reviewed retrospectively. BRAF V600E status was determined by immunohistochemistry (IHC) staining and fluorescence quantitative polymerase chain reaction (PCR). Demographics and MRI characteristics of the two groups were evaluated and compared. Univariate and multivariate Cox regression analyses were performed to identify MRI features that were prognostic for progression-free survival (PFS). RESULTS: T1/FLAIR ratio, enhancing margin, and mean relative apparent diffusion coefficient (rADCmea) value showed significant differences between the BRAF V600E-mutant and BRAF V600E-wild groups (all P < 0.05). Binary logistic regression analysis revealed only rADCmea value was the independent predictive factor for BRAF V600E status (P = 0.027). Univariate Cox regression analysis showed age at diagnosis (P = 0.032), WHO grade (P = 0.020), enhancing margin (P = 0.029), and rADCmea value (P = 0.005) were significant prognostic factors for PFS. In multivariate Cox regression analysis, increasing age (P = 0.040, hazard ratio [HR] = 1.04, 95% confidence interval [CI] = 1.002-1.079) and lower rADCmea values (P = 0.021, HR = 0.036, 95% CI = 0.002-0.602) were associated with poor PFS in GGs and PXAs. CONCLUSION: Imaging features are potentially predictive of BRAF V600E status in GGs and PXAs. Furthermore, rADCmea value is a valuable prognostic factor for patients with GGs or PXAs.

Regeneration of Thyroid Glands in the Spleen Restores Homeostasis in Thyroidectomy Mice.

Surgical removal of the thyroid gland (TG) for treating thyroid disorders leaves the patients on lifelong hormone replacement that partially compensates the physiological needs, but regenerating TG is challenging. Here, an approach is reported to regenerate TG within the spleen for fully restoring the thyroid's functions in mice, by transplanting thyroid tissue blocks to the spleen. Within 48 h, the transplanted tissue efficiently revascularizes, forming thyroid follicles similar to the native gland after 4 weeks. Structurally, the ectopically generated thyroid integrates with the surrounding splenic tissue while maintaining its integrity, separate from the lymphatic tissue. Functionally, it fully restores the native functions of the TG in hormone regulation in response to physiological stimuli, outperforming the established method of oral levothyroxine therapy in maintaining systemic homeostasis. The study demonstrates the full restoration of thyroid functions post-thyroidectomy by intrasplenic TG regeneration, providing fresh insights for designing novel therapies for thyroid-related disorders.

Magnetic resonance imaging radiomics-based prediction of clinically significant prostate cancer in equivocal PI-RADS 3 lesions in the transitional zone.

Purpose: This bi-institutional study aimed to establish a robust model for predicting clinically significant prostate cancer (csPCa) (pathological grade group ≥ 2) in PI-RADS 3 lesions in the transition zone by comparing the performance of combination models. Materials and methods: This study included 243 consecutive men who underwent 3-Tesla magnetic resonance imaging (MRI) and ultrasound-guided transrectal biopsy from January 2020 and April 2022 which is divided into a training cohort of 170 patients and a separate testing cohort of 73 patients. T2WI and DWI images were manually segmented for PI-RADS 3 lesions for the mean ADC and radiomic analysis. Predictive clinical factors were identified using both univariate and multivariate logistic models. The least absolute shrinkage and selection operator (LASSO) regression models were deployed for feature selection and for constructing radiomic signatures. We developed nine models utilizing clinical factors, radiological features, and radiomics, leveraging logistic and XGboost methods. The performances of these models was subsequently compared using Receiver Operating Characteristic (ROC) analysis and the Delong test. Results: Out of the 243 participants with a median age of 70 years, 30 were diagnosed with csPCa, leaving 213 without a csPCa diagnosis. Prostate-specific antigen density (PSAD) stood out as the only significant clinical factor (odds ratio [OR], 1.068; 95% confidence interval [CI], 1.029-1.115), discovered through the univariate and multivariate logistic models. Seven radiomic features correlated with csPCa prediction. Notably, the XGboost model outperformed eight other models (AUC of the training cohort: 0.949, and validation cohort: 0.913). However, it did not surpass the PSAD+MADC model (P > 0.05) in the training and testing cohorts (AUC, 0.949 vs. 0.888 and 0.913 vs. 0.854, respectively). Conclusion: The machine learning XGboost model presented the best performance in predicting csPCa in PI-RADS 3 lesions within the transitional zone. However, the addition of radiomic classifiers did not display any significant enhancement over the compound model of clinical and radiological findings. The most exemplary and generalized option for quantitative prostate evaluation was Mean ADC+PSAD.

Chryseobacterium pyrolae sp. nov., isolated from the rhizosphere soil of Pyrola calliantha H.

A novel Gram-stain-negative, aerobic, non-motile, rod-shaped bacterium, designated pc2-12T, was isolated from the rhizosphere soil of the herb Pyrola calliantha collected from arid areas of Tibet. The strain grew most vigorously with 1 % (w/v) NaCl, at pH 7.0 and at 25 °C. According to the results of 16S rRNA gene sequence analysis, pc2-12T was closely related to the members of the genus Chryseobacterium, with highest levels of sequence similarity to Chryseobacterium viscerum 687B-08T (98.42 %), Chryseobacterium oncorhynchi 701B-08T (98.11 %) and Chryseobacterium ureilyticum DSM 18017T (97.98 %). The average nucleotide identity values between pc2-12T and C. viscerum 687B-08T, C. oncorhynchi 701B-08T and C. ureilyticum DSM 18017T were 79.71, 79.49 and 79.26 %, respectively. The in silico DNA-DNA hybridisation values between pc2-12T and C. viscerum 687B-08T, C. oncorhynchi 701B-08T and C. ureilyticum DSM 18017T were 23.30, 23.00 and 22.90 %, respectively. The draft genome sequence of pc2-12T was 4.64 Mb long, with DNA G+C content of 37.0 mol%. The fatty acids contained in the cells of pc2-12T were mainly composed of iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c). The main polar lipid was phosphatidylethanolamine. MK-6 was the sole respiratory quinone. On the basis of the results of analysis of all the data described, pc2-12T is considered to represent a novel species of the genus Chryseobacterium, for which the name Chryseobacterium pyrolae sp. nov., is proposed. The type strain is pc2-12T (=GDMCC 1.3256T= JCM 35712T).

Cellular senescence: a double-edged sword in cancer therapy.

Over the past few decades, cellular senescence has been identified in cancer patients undergoing chemotherapy and radiotherapy. Senescent cells are generally characterized by permanent cell cycle arrest as a response to endogenous and exogenous stresses. In addition to exiting the cell cycle process, cellular senescence also triggers profound phenotypic changes such as senescence-associated secretory phenotype (SASP), autophagy modulation, or metabolic reprograming. Consequently, cellular senescence is often considered as a tumor-suppressive mechanism that permanently arrests cells at risk of malignant transformation. However, accumulating evidence shows that therapy-induced senescence can promote epithelial-mesenchymal transition and tumorigenesis in neighboring cells, as well as re-entry into the cell cycle and activation of cancer stem cells, thereby promoting cancer cell survival. Therefore, it is particularly important to rapidly eliminate therapy-induced senescent cells in patients with cancer. Here we review the hallmarks of cellular senescence and the relationship between cellular senescence and cancer. We also discuss several pathways to induce senescence in tumor therapy, as well as strategies to eliminate senescent cells after cancer treatment. We believe that exploiting the intersection between cellular senescence and tumor cells is an important means to defeat tumors.

Effect and safety of ultrasound-guided continuous stellate ganglion blockade on neurovascular headache.

OBJECTIVE: To analyze the effect and safety of ultrasound-guided continuous stellate ganglion blockade (CSGB) on neurovascular headache. METHODS: The clinical data of 137 patients with neurovascular headache treated in the First Affiliated Hospital of Hebei North University from March 2019 to October 2021 were analyzed retrospectively. According to the treatment schemes, the patients were assigned to the control group (69 cases, treated with flunarizine combined with Oryzanol tablets), or the observation group (68 cases, treated with ultrasound-guided CSGB on the basis of the treatment to the control group). The efficacy, headache symptoms, negative emotions, cerebral artery blood flow velocity, vasoactive substance levels and adverse reactions of the two groups were compared. Univariate and logistic multivariate analyses were conducted to explore the risk factors for recurrence of neurovascular headache after treatment. RESULTS: The observation group showed a notably higher total effective rate than the control group (95.59% vs. 84.06%, P<0.05). In contrast to the control group, the observation group had notably lower self-rating depression scale (SDS) and Self-Rating Anxiety Scale (SAS) scores and showed notably lower posterior cerebral artery (PCA), middle cerebral artery (MCA), basilar artery (BA) and anterior cerebral artery (ACA) levels (P<0.05). After the treatment, the observation group showed higher levels of serum 5-hydroxy tryptamine (5-HT) and Beta-Endorphin (ß-EP) than the control group, but a lower serum neurotensin (NT) level than the control group. Moreover, the incidence of adverse reactions in the two groups was not greatly different (10.29% vs. 5.80%). The observation group showed a lower recurrence rate within 6 months after treatment than the control group (5.88% vs. 18.84%, P<0.05). Univariate and logistic multivariate analyses showed that occupation (physical labor), smoking history and sleep quality (poor) may be the risk factors for recurrence of neurovascular headache after treatment (OR>1, P<0.05), while CSGB may be the protective factor (OR<1, P<0.05). CONCLUSION: Ultrasound-guided CSGB has obvious analgesic effect on patients with neurovascular headache, which can shorten the duration of headache, improve the cerebral artery blood flow velocity, regulate the levels of vasoactive substances, relieve negative emotions, and lower the recurrence rate, with a high safety.

Improved performance of non-preloaded and high flip-angle dynamic susceptibility contrast perfusion-weighted imaging sequences in the presurgical differentiation of brain lymphoma and glioblastoma.

OBJECTIVE: This study aimed to compare the accuracy of relative cerebral blood volume (rCBV) and percentage signal recovery (PSR) obtained from high flip-angle dynamic susceptibility contrast perfusion-weighted imaging (DSC-PWI) sequences with and without contrast agent (CA) preload for presurgical discrimination of brain glioblastoma and lymphoma. METHODS: Consecutive 336 patients (glioblastoma, 236; PCNSL, 100) were included. All the patients underwent DSC-PWI on 3.0-T magnetic resonance units before surgery. The rCBV and PSR with preloaded and non-preloaded CA were measured. The means of the continuous variables were compared using Welch's t-test. The diagnostic accuracies of the individual parameters were compared using the receiver operating characteristic curve analysis. RESULTS: The rCBV was higher with preloaded CA than with non-preloaded CA (glioblastoma, 10.20 vs. 8.90, p = 0.020; PCNSL, 3.88 vs. 3.27, p = 0.020). The PSR was lower with preloaded CA than with non-preloaded CA (glioblastoma, 0.59 vs. 0.90; PCNSL, 0.70 vs. 1.63; all p < 0.001). Regarding the differentiation of glioblastoma and PCNSL, the AUC of rCBV with preloaded CA was indistinguishable from that of non-preloaded CA (0.940 vs. 0.949, p = 0.703), whereas the area under the curve of PSR with preloaded CA was lower than non-preloaded CA (0.529 vs. 0.884, p < 0.001). CONCLUSION: With preloaded CA, diagnostic performance in differentiating glioblastoma and PCNSL did not improve for rCBV and it was decreased for PSR. Therefore, high flip-angle non-preload DSC-PWI sequences offer excellent accuracy and may be of choice sequence for presurgical discrimination of brain lymphoma and glioblastoma. CLINICAL RELEVANCE STATEMENT: High flip-angle DSC-PWI using non-preloaded CA may be an excellent diagnostic method for distinguishing glioblastoma from PCNSL. KEY POINTS: • Differentiating primary central nervous system lymphoma and glioblastoma accurately is critical for their management. • DSC-PWI sequences optimised for the most accurate CBV calculations may not be the optimal sequences for presurgical brain tumour diagnosis as they could be masquerading leakage phenomena that may provide interesting information in terms of differential diagnosis. • High flip-angle non-preloaded DSC-PWI sequences render the best accuracy in the presurgical differentiation of brain lymphoma and glioblastoma.

Therapeutic strategies targeting AMPK-dependent autophagy in cancer cells.

Macroautophagy is a health-modifying process of engulfing misfolded or aggregated proteins or damaged organelles, coating these proteins or organelles into vesicles, fusion of vesicles with lysosomes to form autophagic lysosomes, and degradation of the encapsulated contents. It is also a self-rescue strategy in response to harsh environments and plays an essential role in cancer cells. AMP-activated protein kinase (AMPK) is the central pathway that regulates autophagy initiation and autophagosome formation by phosphorylating targets such as mTORC1 and unc-51 like activating kinase 1 (ULK1). AMPK is an evolutionarily conserved serine/threonine protein kinase that acts as an energy sensor in cells and regulates various metabolic processes, including those involved in cancer. The regulatory network of AMPK is complicated and can be regulated by multiple upstream factors, such as LKB1, AKT, PPAR, SIRT1, or noncoding RNAs. Currently, AMPK is being investigated as a novel target for anticancer therapies based on its role in macroautophagy regulation. Herein, we review the effects of AMPK-dependent autophagy on tumor cell survival and treatment strategies targeting AMPK.

Phosphorylated PTTG1 switches its subcellular distribution and promotes ß-catenin stabilization and subsequent transcription activity.

The Wnt/ß-catenin signaling is usually abnormally activated in hepatocellular carcinoma (HCC), and pituitary tumor-transforming gene 1 (PTTG1) has been found to be highly expressed in HCC. However, the specific mechanism of PTTG1 pathogenesis remains poorly understood. Here, we found that PTTG1 is a bona fide ß-catenin binding protein. PTTG1 positively regulates Wnt/ß-catenin signaling by inhibiting the destruction complex assembly, promoting ß-catenin stabilization and subsequent nuclear localization. Moreover, the subcellular distribution of PTTG1 was regulated by its phosphorylation status. Among them, PP2A induced PTTG1 dephosphorylation at Ser165/171 residues and prevented PTTG1 translocation into the nucleus, but these effects were effectively reversed by PP2A inhibitor okadaic acid (OA). Interestingly, we found that PTTG1 decreased Ser9 phosphorylation-inactivation of GSK3ß by competitively binding to PP2A with GSK3ß, indirectly leading to cytoplasmic ß-catenin stabilization. Finally, PTTG1 was highly expressed in HCC and associated with poor patient prognosis. PTTG1 could promote the proliferative and metastasis of HCC cells. Overall, our results indicated that PTTG1 plays a crucial role in stabilizing ß-catenin and facilitating its nuclear accumulation, leading to aberrant activation of Wnt/ß-catenin signaling and providing a feasible therapeutic target for human HCC.

Prediction of Ki-67 labeling index, ATRX mutation, and MGMT promoter methylation status in IDH-mutant astrocytoma by morphological MRI, SWI, DWI, and DSC-PWI.

OBJECTIVE: Noninvasive detection of molecular status of astrocytoma is of great clinical significance for predicting therapeutic response and prognosis. We aimed to evaluate whether morphological MRI (mMRI), SWI, DWI, and DSC-PWI could predict Ki-67 labeling index (LI), ATRX mutation, and MGMT promoter methylation status in IDH mutant (IDH-mut) astrocytoma. METHODS: We retrospectively analyzed mMRI, SWI, DWI, and DSC-PWI in 136 patients with IDH-mut astrocytoma.The features of mMRI and intratumoral susceptibility signals (ITSS) were compared using Fisher exact test or chi-square tests. Wilcoxon rank sum test was used to compare the minimum ADC (ADCmin), and minimum relative ADC (rADCmin) of IDH-mut astrocytoma in different molecular markers status. Mann-Whitney U test was used to compare the rCBVmax of IDH-mut astrocytoma with different molecular markers status. Receiver operating characteristic curves was performed to evaluate their diagnostic performances. RESULTS: ITSS, ADCmin, rADCmin, and rCBVmax were significantly different between high and low Ki-67 LI groups. ITSS, ADCmin, and rADCmin were significantly different between ATRX mutant and wild-type groups. Necrosis, edema, enhancement, and margin pattern were significantly different between low and high Ki-67 LI groups. Peritumoral edema was significantly different between ATRX mutant and wild-type groups. Grade 3 IDH-mut astrocytoma with unmethylated MGMT promoter was more likely to show enhancement compared to the methylated group. CONCLUSIONS: mMRI, SWI, DWI, and DSC-PWI were shown to have the potential to predict Ki-67 LI and ATRX mutation status in IDH-mut astrocytoma. A combination of mMRI and SWI may improve diagnostic performance for predicting Ki-67 LI and ATRX mutation status. CLINICAL RELEVANCE STATEMENT: Conventional MRI and functional MRI (SWI, DWI, and DSC-PWI) can predict Ki-67 expression and ATRX mutation status of IDH mutant astrocytoma, which may help clinicians determine personalized treatment plans and predict patient outcomes. KEY POINTS: • A combination of multimodal MRI may improve the diagnostic performance to predict Ki-67 LI and ATRX mutation status. • Compared with IDH-mutant astrocytoma with low Ki-67 LI, IDH-mutant astrocytoma with high Ki-67 LI was more likely to show necrosis, edema, enhancement, poorly defined margin, higher ITSS levels, lower ADC, and higher rCBV. • ATRX wild-type IDH-mutant astrocytoma was more likely to show edema, higher ITSS levels, and lower ADC compared to ATRX mutant IDH-mutant astrocytoma.

Whole-tumor histogram analysis of diffusion and perfusion metrics for noninvasive pediatric glioma grading.

PURPOSE: An accurate assessment of the World Health Organization grade is vital for patients with pediatric gliomas to direct treatment planning. We aim to evaluate the diagnostic performance of whole-tumor histogram analysis of diffusion-weighted imaging (DWI) and dynamic susceptibility contrast-enhanced perfusion-weighted imaging (DSC-PWI) for differentiating pediatric high-grade gliomas from pediatric low-grade gliomas. METHODS: Sixty-eight pediatric patients (mean age, 10.47 ± 4.37 years; 42 boys) with histologically confirmed gliomas underwent preoperative MR examination. The conventional MRI features and whole-tumor histogram features extracted from apparent diffusion coefficient (ADC) and cerebral blood volume (CBV) maps were analyzed, respectively. Receiver operating characteristic curves and the binary logistic regression analysis were performed to determine the diagnostic performance of parameters. RESULTS: For conventional MRI features, location, hemorrhage and tumor margin showed significant difference between pediatric high- and low-grade gliomas (all, P < .05). For advanced MRI parameters, ten histogram features of ADC and CBV showed significant differences between pediatric high- and low-grade gliomas (all, P < .05). The diagnostic performance of the combination of DSC-PWI and DWI (AUC = 0.976, sensitivity = 100%, NPV = 100%) is superior to conventional MRI or DWI model, respectively (AUCcMRI = 0.700, AUCDWI = 0.830; both, P < .05). CONCLUSION: The whole-tumor histogram analysis of DWI and DSC-PWI is a promising method for grading pediatric gliomas.