Survival Outcome Prediction in Glioblastoma: Insights from MRI Radiomics.

Background: Extracting multiregional radiomic features from multiparametric MRI for predicting pretreatment survival in isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM) patients is a promising approach. Methods: MRI data from 49 IDH wild-type glioblastoma patients pre-treatment were utilized. Diffusion and perfusion maps were generated, and tumor subregions segmented. Radiomic features were extracted for each tissue type and map. Feature selection on 1862 radiomic features identified 25 significant features. The Cox proportional-hazards model with LASSO regularization was used to perform survival analysis. Internal and external validation used a 38-patient training cohort and an 11-patient validation cohort. Statistical significance was set at p < 0.05. Results: Age and six radiomic features (shape and first and second order) from T1W, diffusion, and perfusion maps contributed to the final model. Findings suggest that a small necrotic subregion, inhomogeneous vascularization in the solid non-enhancing subregion, and edema-related tissue damage in the enhancing and edema subregions are linked to poor survival. The model's C-Index was 0.66 (95% C.I. 0.54-0.80). External validation demonstrated good accuracy (AUC > 0.65) at all time points. Conclusions: Radiomics analysis, utilizing segmented perfusion and diffusion maps, provide predictive indicators of survival in IDH wild-type glioblastoma patients, revealing associations with microstructural and vascular heterogeneity in the tumor.

Pituitary gland height evaluated with magnetic resonance imaging in premature twins: the impact of growth and sex.

BACKGROUND: Pituitary gland height reflects secretory activity of the hypothalamo-pituitary axis. OBJECTIVE: To assess the cumulative impact of fetal growth and sex on pituitary gland height in premature twins, dissociated from prematurity. MATERIALS AND METHODS: A retrospective study was conducted, assessing the pituitary gland height in 63 pairs of preterm twins, measured from T1-weighted magnetic resonance imaging (MRI). Auxological parameters, including body weight, body length, and head circumference, at birth and at the time of MRI, were used as proxies for fetal and postnatal growth, respectively. The study population was divided into two groups, using corrected age at around term equivalent as the cutoff point. Statistical analysis was performed using mixed-effects linear regression models. RESULTS: When pituitary gland height was evaluated at around term equivalent, a greater pituitary gland height, suggesting a more immature hypothamo-pituitary axis, was associated with the twin exhibiting lower auxological data at birth. The same association was observed when body weight and length at MRI were used as covariants. In the group evaluated after term equivalent, a smaller pituitary gland height, suggesting a more mature hypothamo-pituitary axis, was associated with male sex. This difference was observed in twin pairs with higher average body weight at birth, and in babies exhibiting higher auxological data at MRI. CONCLUSION: After isolating the effect of prematurity, at around term equivalent, pituitary gland height reflects the cumulative impact of fetal growth on the hypothalamo-pituitary axis. Subsequently, pituitary gland height shows effects of sex and of fetal and postnatal growth.

Can maternal hormones play a significant role in delivery mode?

The aim of this study was primarily to evaluate the levels of progesterone, oestradiol and relaxin during different delivery modes and secondarily to assess specific traits and changes in maternal pelvic dimensions during pregnancy and childbirth, in correlation with foetal size and maternal hormonal profile. Nulliparous women (n = 448) were evaluated at three different stages, during first trimester, at the time of admission for childbirth and finally just before childbirth. Each examination included clinical internal pelvimetry, blood sample collection for defining the hormones levels in peripheral maternal circulation and ultrasonographic measurements of specific variables of the pubic symphysis and the foetus. We included 304 nulliparous women divided in three groups. According to our results, there was statistically significant difference at the mean progesterone, oestradiol and relaxin range during different modes of childbirth (p-value < .01). We also found significant correlation between the newborn's weight and the changes in pubic symphysis dimensions. However, no significant association was noted between maternal hormones studied and the changes in pelvic dimensions.IMPACT STATEMENTWhat is already known on this subject? Mode of childbirth can be affected by various aspects, like maternal pelvic anatomy, foetal size and hormonal status at the time of labour. Hormonal fluctuations along with mechanical forces caused by the foetus are believed to lead to morphological alterations to promote natural vaginal childbirth.What do the results of this study add? Our results clearly showed that successful vaginal delivery is characterised by the prevalence of a hyperoestrogenic environment with higher values of intrapartum oestradiol range and significant increase in maternal serum relaxin levels. We also proved that progesterone levels do not decrease during vaginal childbirth, and we concluded that foetal size seems to be the most crucial factor causing alterations in maternal pelvis during parturition.What are the implications of these findings for clinical practice and further research? Our findings could form part of a set of key factors included in future algorithms or computerised biomechanical models for predicting potential childbirth mode. Larger multicenter studies should confirm our results and evaluate their clinical significance in the decision making to ensure safe childbirth and optimal maternal and perinatal outcomes.

Structural and functional brain connectivity in moderate-late preterm infants with low-grade intraventricular hemorrhage.

PURPOSE: Brain functional connectivity (FC) changes and microstructural abnormalities are reported in infants born moderate and late preterm (MLPT). We evaluated the effect of low-grade (grades I, II) intraventricular hemorrhage (IVH) in MLPT babies on brain structural connectivity (SC) and FC. METHODS: Babies born MLPT between January 2014 and May 2017 underwent brain ultrasound (US) at 72 h and 7 days after birth, and MRI at around term equivalent. The MRI protocol comprised T1- and T2-weighted sequences, diffusion tensor imaging (DTI), and resting-state functional MRI (fMRI). SC and FC were assessed using graph analysis. RESULTS: Of 350 MLPT neonates, 15 showed low-grade IVH on US at 72 h, for which brain MRI was available in 10. These 10 infants, with mean gestational age (GA) 34.0 ± 0.8 weeks, comprised the study group, and 10 MLPT infants of mean GA 33.9 ± 1.1 weeks, with no abnormalities on brain US and MRI, were control subjects. All study subjects presented modularity, small world topology, and rich club organization for both SC and FC. The patients with low-grade IVH had lower FC rich club coefficient and lower SC betweenness centrality in the left frontoparietal operculum, and lower SC rich club coefficient in the right superior orbitofrontal cortex than the control subjects. CONCLUSIONS: Topological and functional properties of mature brain connectivity are present in MLPT infants. IVH in these infants was associated with structural and functional abnormalities in the left frontoparietal operculum and right orbitofrontal cortex, regions related to language and cognition.

Functional connectivity and microstructural changes of the brain in primary Sjögren syndrome: the relationship with depression.

BACKGROUND: Fatigue and depression are among the most common manifestations of primary Sjögren syndrome (pSS), but information is lacking on the relationship with brain function and microstructural changes. PURPOSE: To investigate microstructural changes and brain connectivity in pSS, and to evaluate their relationship with fatigue and depression. MATERIAL AND METHODS: The study included 29 patients with pSS (mean age 61.2 ± 12.1 years; disease duration 10.5 ± 5.9 years) and 28 controls (mean age 58.4 ± 9.2 years). All the patients completed the Beck's depression and Fatigue Assessment Scale questionnaires. The imaging protocol consisted of: (i) standard magnetic resonance imaging (MRI) pulse sequences (FLAIR, 3D T1W); (ii) a diffusion tensor imaging pulse sequence; and (iii) a resting state functional MRI pulse sequence. Resting state brain networks and maps of diffusion metrics were calculated and compared between patients and controls. RESULTS: Compared with the controls, the patients with pSS and depression showed increased axial, radial, and mean diffusivity and decreased fractional anisotropy; those without depression showed decreased axial diffusivity in major white matter tracts (superior longitudinal fasciculus, inferior longitudinal fasciculus, corticospinal tract, anterior thalamic radiation, inferior fronto-occipital fasciculus, cingulum, uncinate fasciculus, and forceps minor-major). Decreased brain activation in the sensorimotor network was observed in the patients with pSS compared with the controls. No correlation was found between fatigue and structural or functional changes of the brain. CONCLUSION: pSS is associated with functional connectivity abnormalities of the somatosensory cortex and microstructural abnormalities in major white matter tracts, which are more pronounced in depression.

Functional and structural connectivity of the brain in very preterm babies: relationship with gestational age and body and brain growth.

BACKGROUND: Structural and functional changes of the brain have been reported in premature babies. OBJECTIVE: To evaluate the relationship of functional and structural connectivity with gestational age, body growth and brain maturation in very preterm babies. MATERIALS AND METHODS: We studied 18 very preterm babies (gestational age: mean ± standard deviation, 29.7±1.7 weeks). We examined functional connectivity by multivariate pattern analysis of resting-state functional MRI data. We assessed structural connectivity by analysis of diffusion tensor imaging data and probabilistic tractography. RESULTS: The average functional connectivity of the medial orbitofrontal cortex with the rest of the brain was positively associated with gestational age (P<0.001). Fractional anisotropy of the right inferior fronto-occipital fasciculus was positively associated with head circumference at term-equivalent age. Structural connectivity of the inferior fronto-occipital fasciculus with the medial orbitofrontal cortex was positively associated with head circumference at term-equivalent age. Body weight at term-equivalent age was the only independent predictor of average structural connectivity of the medial orbitofrontal cortex with the rest of the brain (P=0.020). CONCLUSION: Structural and functional connectivity of the medial orbitofrontal cortex with the rest of the brain depend on body growth and degree of prematurity, respectively.

Liver perivascular epithelioid cell tumor in a patient with systemic lupus erythematosus.

INTRODUCTION: Perivascular epithelioid cell tumor (PECOMA) is a rare mesenchymal neoplasm which expresses both myogenic and melanocytic markers showing a benign course,although malignant tumors have also been reported. To date there are approximately 33 cases of published hepatic pecomas. PRESENTATION OF CASE: We describe a 47-year-old man with a 27-year past medical history of systemic lupus erythematosus (SLE) who underwent left liver lobectomy due to a liver pecoma. His postoperative course complicated with infection, thrombosis of hepatic artery and liver ischemia as well as drug fever. DISCUSSION: Treatment protocol especially for hepatic PECOMA has not reached a consensus although surgical resection is the preferred therapy. CONCLUSION: This is the first case of coexistence of liver pecoma and SLE.

Pseudoexfoliation syndrome without glaucoma: White matter abnormalities detected by conventional MRI and diffusion tensor imaging.

PURPOSE: To assess macro- and microstructural brain changes in patients with pseudoexfoliation syndrome (PXS). MATERIALS AND METHODS: Comprehensive ophthalmic examination and brain MRI were conducted on 20 patients with PXS without glaucoma (aged 62.75 ±â€¯0.4 years) and 20 controls (aged 62 ±â€¯0.6 years). White matter (WM) integrity was evaluated on FLAIR and single-shot multisection SE-EPI diffusion tensor imaging (DTI) sequences. The presence and the number of white matter hyperintensities (WMHIs) on FLAIR images was compared between all patients and control subjects. Microstructural WM changes on DTI was evaluated using Tract-based spatial statistics (TBSS). DTI metrics of the optic tracts were assessed by the region-of-interest (ROI) method. RESULTS: A significantly higher number of WMHIs was found in the patients with PXS than in the control subjects (P ≤ 0.002). On DTI the patients showed bilateral increase in the mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) values in the anterior thalamic radiation, the inferior fronto-occipital fasciculus, the superior longitudinal fasciculus, the inferior longitudinal fasciculus and the forceps minor. TBSS revealed no significant difference in fractional anisotropy (FA) values, but ROIs analysis of the optic tracts revealed decreased FA values in the patients. CONCLUSION: MRI in patients with PXS detects abnormalities in the brain and the optic tracts at a subclinical stage. Early detection of microstructural changes could be useful to guide appropriate treatment to impede the disease process.

The association between multiple sclerosis and spondylosis: When and why.

OBJECTIVES: To evaluate risk factors for the development of cervical spine spondylosis (CSS) in patients with multiple sclerosis (MS) and to propose a pathogenetic mechanism. METHODS: Forty-two consecutive patients aged 23-66 years with MS and 42 age and sex matched controls were evaluated retrospectively; Clinical disability was evaluated with the expanded disability status scale (EDSS) and spasticity with the Asworth score. Total brain lesion volume (BLV), total grey matter (GM) volume and deep GM volume were assessed. In the cervical spine CSS indices (disk dehydration, disk protrusion, abnormal posture and osteophytosis) and the spinal cord lesion load (SLL) was evaluated. The association of CSS indices with the presence of MS, the clinical scales and the brain and spinal cord imaging measurements were assessed. RESULTS: Presence of MS was positively associated with abnormal posture (P=0.002), disk dehydration at C6-C7 (P=0.049) and posterior disk protrusion at C5-C6 (P=0.033) and C6-C7 (P=0.001). All patients had spasticity. Patients with abnormal posture were younger (37.5±11.1years) than those with normal (45.4±8.6years), P=0.024. Age (P=0.008), EDSS (P=0.045) and BLV (P=0.084) were significant independent predictors of abnormal posture. Younger age combined with worse EDSS and increased BLV predicted abnormal posture. CONCLUSIONS: Patients with MS present more frequently spondylosis which is associated with younger age, more severe disability and extensive lesions in the brain. Spasticity induced by the brain lesions and abnormal expression of extracellular matrix proteins in the brain and the intervertebral disk constitute a possible pathogenetic mechanism.

The role of diffusion tensor imaging and dynamic susceptibility perfusion MRI in the evaluation of meningioma grade and subtype.

PURPOSE: We prospectively investigated the relationship between diffusion tensor imaging (DTI), dynamic susceptibility perfusion (DSP) MRI metrics and grade, subtype and Ki-67 labelling index of meningiomas. MATERIALS AND ΜETHODS: Thirty-nine patients operated for meningioma were included in the study. DTI and DSP were performed within a week prior to surgical excision. Lesion/normal (L/N) tissue ratios and peritumoral area/normal tissue (P/N) ratios were calculated for the apparent diffusion coefficient (ADC), fractional anisotropy (FA) and relative cerebral blood volume (rCBV). In the tumor specimens Ki-67 antigen expression was evaluated by the MIB-1 immunostaining method. RESULTS: There were 31 grade I, 7 grade II and one grade III meningiomas. Grade I meningiomas had a significantly lower L/N rCBV ratios than grade II/III meningiomas (median 5.1 vs 6.4, p=0.031). Grade I meningiomas revealed significantly lower P/N rCBV ratios than grade II/III meningiomas (median 0.78 vs 1.1, p=0.0077). Grade I meningiomas had significantly higher FA ratios than grade II/III meningiomas (median 0.5 vs 0.31, p=0.012). Meningiomas of meningothelial type had a significantly higher L/N rCBV ratio than other grade I meningiomas (median 5.4 vs 3.8, p=0.0136). There was no significant correlation between rCBV, ADC, FA and Ki-67 index. CONCLUSION: Dynamic susceptibility perfusion indexes in lesion/normal and peritumoral/normal tissue ratios are useful for the differentiation grade I from grade II/III menigiomas. Meningothelial meningiomas showed higher lesion/normal tissue rCBV ratios from the other benign meningioma subtypes.

Diffusion tensor imaging in children with tuberous sclerosis complex: tract-based spatial statistics assessment of brain microstructural changes.

BACKGROUND: There is evidence of microstructural changes in normal-appearing white matter of patients with tuberous sclerosis complex. OBJECTIVE: To evaluate major white matter tracts in children with tuberous sclerosis complex using tract-based spatial statistics diffusion tensor imaging (DTI) analysis. MATERIALS AND METHODS: Eight children (mean age ± standard deviation: 8.5 ± 5.5 years) with an established diagnosis of tuberous sclerosis complex and 8 age-matched controls were studied. The imaging protocol consisted of T1-weighted high-resolution 3-D spoiled gradient-echo sequence and a spin-echo, echo-planar diffusion-weighted sequence. Differences in the diffusion indices were evaluated using tract-based spatial statistics. RESULTS: Tract-based spatial statistics showed increased axial diffusivity in the children with tuberous sclerosis complex in the superior and anterior corona radiata, the superior longitudinal fascicle, the inferior fronto-occipital fascicle, the uncinate fascicle and the anterior thalamic radiation. No significant differences were observed in fractional anisotropy, mean diffusivity and radial diffusivity between patients and control subjects. No difference was found in the diffusion indices between the baseline and follow-up examination in the patient group. CONCLUSION: Patients with tuberous sclerosis complex have increased axial diffusivity in major white matter tracts, probably related to reduced axonal integrity.

Correlation of diffusion tensor and dynamic susceptibility contrast MRI with DNA ploidy and cell cycle analysis of gliomas.

OBJECTIVES: Flow cytometry provides a powerful tool to assess cells in G0/G1, S and G2/M phase and ploidy. The purpose of the present study was to investigate the correlation between diffusion tensor (DTI) and dynamic susceptibility contrast (DSC) MRI metrics with cell cycle analysis findings in gliomas. PATIENTS AND METHODS: We studied thirty patients who were operated on for glioma. DTI and DSC MRI were performed within a week prior to surgical excision. Lesion/normal ratios were calculated for the ADC, FA and rCBV. In an excised tumour sample flow cytometric analysis was performed. RESULTS: There were 24 glioblastomas, 2 anaplastic astrocytomas, 1 oligoastrocytoma and 3 diffuse astrocytomas. There were significant differences between low and high-grade gliomas for rCBV and ADC values. Low grade tumours had higher G0/G1 phase fraction and lower S-phase, G2/M, S+G2/M and S+G2/M/G0/G1 fractions There was a significant negative correlation between rCBV and G0/G1 phase fraction and a positive correlation with G2/M, S+G2/M and the S+G2/M/G0/G1 fraction. Significant correlation was also observed between FA ratio and S+G2/M/G0/G1. There was a negative significant correlation between ADC and S+G2/M and the S+G2/M/G0/G1 fraction. There were 21 (70%) diploid and 9 (30%) aneuploid tumours. No significant difference was found between diploid and aneuploid tumours with respect to rCBV, ADC and FA values. CONCLUSION: Dynamic susceptibility contrast MRI and diffusion tensor imaging metrics are correlated to tumour aggressiveness as assessed by cell cycle analysis.

Brain growth in preterm infants is affected by the degree of growth restriction at birth.

OBJECTIVE: Documentation of examination of brain structural development by magnetic resonance imaging (MRI) beyond the neonatal period is scarce for both preterm and small for gestational age (SGA) infants. AIM: To investigate structural brain development during infancy in preterm children born SGA by MRI. METHODS: A total of 205 preterm infants, 139 appropriate for gestational age (AGA) and 66 SGA, of which 33 had birth weight (BW) < 3rd percentile and 33 had BW 3rd-10th percentile, were examined prospectively by brain MRI at the corrected age of 5 months. The total volume of the brain, ventricles and cerebellum, the area of vermis and corpus callosum, and the height of the pituitary, mesencephalon and pons were estimated on MRI. RESULTS: Brain volume was smaller in the SGA < 3rd percentile infants, independent of other perinatal factors. Chronic lung disease was an independent predictor of low brain volume. Pituitary height was greater in SGA < 3rd percentile than in AGA infants. The corpus callosum area was less in SGA < 3rd percentile than in SGA of 3rd-10th percentile infants. CONCLUSIONS: Preterm infants born SGA with BW < 3rd percentile had differences in brain structural measurements at the corrected age of 5 months, compared with preterm AGA infants, which could have implications for their neurocognitive development.