Deep learning links localized digital pathology phenotypes with transcriptional subtype and patient outcome in glioblastoma.

BACKGROUND: Deep learning has revolutionized medical image analysis in cancer pathology, where it had a substantial clinical impact by supporting the diagnosis and prognostic rating of cancer. Among the first available digital resources in the field of brain cancer is glioblastoma, the most common and fatal brain cancer. At the histologic level, glioblastoma is characterized by abundant phenotypic variability that is poorly linked with patient prognosis. At the transcriptional level, 3 molecular subtypes are distinguished with mesenchymal-subtype tumors being associated with increased immune cell infiltration and worse outcome. RESULTS: We address genotype-phenotype correlations by applying an Xception convolutional neural network to a discovery set of 276 digital hematozylin and eosin (H&E) slides with molecular subtype annotation and an independent The Cancer Genome Atlas-based validation cohort of 178 cases. Using this approach, we achieve high accuracy in H&E-based mapping of molecular subtypes (area under the curve for classical, mesenchymal, and proneural = 0.84, 0.81, and 0.71, respectively; P < 0.001) and regions associated with worse outcome (univariable survival model P < 0.001, multivariable P = 0.01). The latter were characterized by higher tumor cell density (P < 0.001), phenotypic variability of tumor cells (P < 0.001), and decreased T-cell infiltration (P = 0.017). CONCLUSIONS: We modify a well-known convolutional neural network architecture for glioblastoma digital slides to accurately map the spatial distribution of transcriptional subtypes and regions predictive of worse outcome, thereby showcasing the relevance of artificial intelligence-enabled image mining in brain cancer.

Acute impact of posthemorrhagic ventricular dilatation on cerebral oxygenation in preterm infants with intraventricular haemorrhage.

AIM: To assess the effect of ventricular decompression on cerebral oxygenation in preterm neonates with intraventricular haemorrhage (IVH) and posthemorrhagic ventricular dilatation (PHVD) using near-infrared spectroscopy (NIRS). METHODS: Fifty-three preterm neonates born <34 weeks' gestation between 2013 and 2023 with IVH and subsequent PHVD were prospectively included. Regional cerebral oxygen saturation (rScO2) as well as fractional cerebral tissue oxygen extraction (cFTOE) were analysed 2 weeks before and after ventricular decompression. RESULTS: Ventricular decompression was performed at 18 ± 6 days of life. Patients with repeated lumbar punctures prior to ventricular drainage showed consistently higher rScO2 and lower cFTOE levels 2 weeks before and after intervention compared to those without. Patients who underwent direct ventricular drainage showed an immediate increase in rScO2 levels on the day of the procedure. In patients who underwent prior lumbar punctures, ventricular decompression did not yield additional acute effects on cerebral oxygenation. CONCLUSION: Patients who underwent repeated lumbar punctures preceding ventricular drainage consistently maintained higher rScO2 and lower cFTOE levels during the study period. In these patients, ventricular decompression did not further affect cerebral oxygenation, as they already demonstrated improved cerebral hemodynamics, whereas an immediate improvement was observed in those without prior lumbar punctures.

Contrast Agent Dynamics Determine Radiomics Profiles in Oncologic Imaging.

BACKGROUND: The reproducibility of radiomics features extracted from CT and MRI examinations depends on several physiological and technical factors. The aim was to evaluate the impact of contrast agent timing on the stability of radiomics features using dynamic contrast-enhanced perfusion CT (dceCT) or MRI (dceMRI) in prostate and lung cancers. METHODS: Radiomics features were extracted from dceCT or dceMRI images in patients with biopsy-proven peripheral prostate cancer (pzPC) or biopsy-proven non-small cell lung cancer (NSCLC), respectively. Features that showed significant differences between contrast phases were identified using linear mixed models. An L2-penalized logistic regression classifier was used to predict class labels for pzPC and unaffected prostate regions-of-interest (ROIs). RESULTS: Nine pzPC and 28 NSCLC patients, who were imaged with dceCT and/or dceMRI, were included in this study. After normalizing for individual enhancement patterns by defining seven individual phases based on a reference vessel, 19, 467 and 128 out of 1204 CT features showed significant temporal dynamics in healthy prostate parenchyma, prostate tumors and lung tumors, respectively. CT radiomics-based classification accuracy of healthy and tumor ROIs was highly dependent on contrast agent phase. For dceMRI, 899 and 1027 out of 1118 features were significantly dependent on time after contrast agent injection for prostate and lung tumors. CONCLUSIONS: CT and MRI radiomics features in both prostate and lung tumors are significantly affected by interindividual differences in contrast agent dynamics.

Towards the adoption of quantitative computed tomography in the management of interstitial lung disease.

The shortcomings of qualitative visual assessment have led to the development of computer-based tools to characterise and quantify disease on high-resolution computed tomography (HRCT) in patients with interstitial lung diseases (ILDs). Quantitative CT (QCT) software enables quantification of patterns on HRCT with results that are objective, reproducible, sensitive to change and predictive of disease progression. Applications developed to provide a diagnosis or pattern classification are mainly based on artificial intelligence. Deep learning, which identifies patterns in high-dimensional data and maps them to segmentations or outcomes, can be used to identify the imaging patterns that most accurately predict disease progression. Optimisation of QCT software will require the implementation of protocol standards to generate data of sufficient quality for use in computerised applications and the identification of diagnostic, imaging and physiological features that are robustly associated with mortality for use as anchors in the development of algorithms. Consortia such as the Open Source Imaging Consortium have a key role to play in the collation of imaging and clinical data that can be used to identify digital imaging biomarkers that inform diagnosis, prognosis and response to therapy.

Improving Vessel Segmentation with Multi-Task Learning and Auxiliary Data Available Only During Model Training.

Liver vessel segmentation in magnetic resonance imaging data is important for the computational analysis of vascular remodeling, associated with a wide spectrum of diffuse liver diseases. Existing approaches rely on contrast enhanced imaging data, but the necessary dedicated imaging sequences are not uniformly acquired. Images without contrast enhancement are acquired more frequently, but vessel segmentation is challenging, and requires large-scale annotated data. We propose a multi-task learning framework to segment vessels in liver MRI without contrast. It exploits auxiliary contrast enhanced MRI data available only during training to reduce the need for annotated training examples. Our approach draws on paired native and contrast enhanced data with and without vessel annotations for model training. Results show that auxiliary data improves the accuracy of vessel segmentation, even if they are not available during inference. The advantage is most pronounced if only few annotations are available for training, since the feature representation benefits from the shared task structure. A validation of this approach to augment a model for brain tumor segmentation confirms its benefits across different domains. An auxiliary informative imaging modality can augment expert annotations even if it is only available during training.

Predicting dynamic, motion-related changes in B0 field in the brain at a 7T MRI using a subject-specific fine-trained U-net.

PURPOSE: Subject movement during the MR examination is inevitable and causes not only image artifacts but also deteriorates the homogeneity of the main magnetic field (B0 ), which is a prerequisite for high quality data. Thus, characterization of changes to B0 , for example induced by patient movement, is important for MR applications that are prone to B0 inhomogeneities. METHODS: We propose a deep learning based method to predict such changes within the brain from the change of the head position to facilitate retrospective or even real-time correction. A 3D U-net was trained on in vivo gradient-echo brain 7T MRI data. The input consisted of B0 maps and anatomical images at an initial position, and anatomical images at a different head position (obtained by applying a rigid-body transformation on the initial anatomical image). The output consisted of B0 maps at the new head positions. We further fine-trained the network weights to each subject by measuring a limited number of head positions of the given subject, and trained the U-net with these data. RESULTS: Our approach was compared to established dynamic B0 field mapping via interleaved navigators, which suffer from limited spatial resolution and the need for undesirable sequence modifications. Qualitative and quantitative comparison showed similar performance between an interleaved navigator-equivalent method and proposed method. CONCLUSION: It is feasible to predict B0 maps from rigid subject movement and, when combined with external tracking hardware, this information could be used to improve the quality of MR acquisitions without the use of navigators.

Metabolic tumor volume and sites of organ involvement predict outcome in NSCLC immune-checkpoint inhibitor therapy.

PURPOSE: The purpose of this study was to assess the ability of pretreatment PET parameters and peripheral blood biomarkers to predict progression-free survival (PFS) and overall survival (OS) in NSCLC patients treated with ICIT. METHODS: We prospectively included 87 patients in this study who underwent pre-treatment [18F]-FDG PET/CT. Organ-specific and total metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured using a semiautomatic software. Sites of organ involvement (SOI) were assessed by PET/CT. The log-rank test and Cox-regression analysis were used to assess associations between clinical, laboratory, and imaging parameters with PFS and OS. Time dependent ROC were calculated and model performance was evaluated in terms of its clinical utility. RESULTS: MTV increased with the number of SOI and was correlated with neutrophil and lymphocyte cell count (Spearman's rho = 0.27 or 0.32; p =.02 or 0.003; respectively). Even after adjustment for known risk factors, such as PD-1 expression and neutrophil cell count, the MTV and the number of SOI were independent risk factors for progression (per 100 cm3; adjusted hazard ratio [aHR]: 1.13; 95% confidence interval [95%CI]: 1.01-1.28; p =.04; single SOI vs. ≥ 4 SOI: aHR: 2.26, 95%CI: 1.04-4.94; p =.04). MTV and the number of SOI were independent risk factors for overall survival (per 100 cm3 aHR: 1.11, 95%CI: 1.01-1.23; p =.03; single SOI vs. ≥ 4 SOI: aHR: 4.54, 95%CI: 1.64-12.58; p =.04). The combination of MTV and the number of SOI improved the risk stratification for PFS and OS (log-rank test p <.001; C-index: 0.64 and 0.67). CONCLUSION: The MTV and the number of SOI are simple imaging markers that provide complementary information to facilitate risk stratification in NSCLC patients scheduled for ICIT.

Artificial intelligence in medical imaging is a tool for clinical routine and scientific discovery.

The emergence of powerful machine learning methodology together with an increasing amount of data collected during clinical routine have fostered a growing role of artificial intelligence (AI) in medicine. Algorithms have become part of clinical care enhancing image reconstruction, detecting cancer or predicting individual risk to support treatment decisions and patient management. The entry into clinical care is determined by technological feasibility, integration into effective workflows, and immediacy of benefits. At the same time, research is advancing the integration of imaging data and other modalities such as genomics, and the linking of observations made at large scale with the understanding of underlying biological processes. AI will have impact in imaging and precision medicine not only because of the successful application of techniques established in other domains, but primarily because of the effective joint development of new technology and corresponding advance of diagnosis and care.

Current and Future Perspectives on Computed Tomography Screening for Lung Cancer: A Roadmap From 2023 to 2027 From the International Association for the Study of Lung Cancer.

Low-dose computed tomography (LDCT) screening for lung cancer substantially reduces mortality from lung cancer, as revealed in randomized controlled trials and meta-analyses. This review is based on the ninth CT screening symposium of the International Association for the Study of Lung Cancer, which focuses on the major themes pertinent to the successful global implementation of LDCT screening and develops a strategy to further the implementation of lung cancer screening globally. These recommendations provide a 5-year roadmap to advance the implementation of LDCT screening globally, including the following: (1) establish universal screening program quality indicators; (2) establish evidence-based criteria to identify individuals who have never smoked but are at high-risk of developing lung cancer; (3) develop recommendations for incidentally detected lung nodule tracking and management protocols to complement programmatic lung cancer screening; (4) Integrate artificial intelligence and biomarkers to increase the prediction of malignancy in suspicious CT screen-detected lesions; and (5) standardize high-quality performance artificial intelligence protocols that lead to substantial reductions in costs, resource utilization and radiologist reporting time; (6) personalize CT screening intervals on the basis of an individual's lung cancer risk; (7) develop evidence to support clinical management and cost-effectiveness of other identified abnormalities on a lung cancer screening CT; (8) develop publicly accessible, easy-to-use geospatial tools to plan and monitor equitable access to screening services; and (9) establish a global shared education resource for lung cancer screening CT to ensure high-quality reading and reporting.

Radiomic features define risk and are linked to DNA methylation attributes in primary CNS lymphoma.

Background: The prognostic roles of clinical and laboratory markers have been exploited to model risk in patients with primary CNS lymphoma, but these approaches do not fully explain the observed variation in outcome. To date, neuroimaging or molecular information is not used. The aim of this study was to determine the utility of radiomic features to capture clinically relevant phenotypes, and to link those to molecular profiles for enhanced risk stratification. Methods: In this retrospective study, we investigated 133 patients across 9 sites in Austria (2005-2018) and an external validation site in South Korea (44 patients, 2013-2016). We used T1-weighted contrast-enhanced MRI and an L1-norm regularized Cox proportional hazard model to derive a radiomic risk score. We integrated radiomic features with DNA methylation profiles using machine learning-based prediction, and validated the most relevant biological associations in tissues and cell lines. Results: The radiomic risk score, consisting of 20 mostly textural features, was a strong and independent predictor of survival (multivariate hazard ratio = 6.56 [3.64-11.81]) that remained valid in the external validation cohort. Radiomic features captured gene regulatory differences such as in BCL6 binding activity, which was put forth as testable treatment target for a subset of patients. Conclusions: The radiomic risk score was a robust and complementary predictor of survival and reflected characteristics in underlying DNA methylation patterns. Leveraging imaging phenotypes to assess risk and inform epigenetic treatment targets provides a concept on which to advance prognostic modeling and precision therapy for this aggressive cancer.

Cortical thickness in the right medial frontal gyrus predicts planning performance in healthy children and adolescents.

The ability to plan is an important part of the set of the cognitive skills called "executive functions." To be able to plan actions in advance is of great importance in everyday life and constitutes one of the major key features for academic as well as economic success. The present study aimed to investigate the neuroanatomical correlates of planning in normally developing children, as measured by the cortical thickness of the prefrontal cortex. Eighteen healthy children and adolescents underwent structural MRI examinations and the Tower of London (ToL) task. A multiple regression analysis revealed that the cortical thickness of the right caudal middle frontal gyrus (cMFG) was a significant predictor of planning performance. Neither the cortical thickness of any other prefrontal area nor gender were significantly associated with performance in the ToL task. The results of the present exploratory study suggest that the cortical thickness of the right, but not the left cMFG, is positively correlated with performance in the ToL task. We, therefore, conclude that increased cortical thickness may be more beneficial for higher-order processes, such as information integration, than for lower-order processes, such as the analysis of external information.

Correlation of histologic, imaging, and artificial intelligence features in NAFLD patients, derived from Gd-EOB-DTPA-enhanced MRI: a proof-of-concept study.

OBJECTIVE: To compare unsupervised deep clustering (UDC) to fat fraction (FF) and relative liver enhancement (RLE) on Gd-EOB-DTPA-enhanced MRI to distinguish simple steatosis from non-alcoholic steatohepatitis (NASH), using histology as the gold standard. MATERIALS AND METHODS: A derivation group of 46 non-alcoholic fatty liver disease (NAFLD) patients underwent 3-T MRI. Histology assessed steatosis, inflammation, ballooning, and fibrosis. UDC was trained to group different texture patterns from MR data into 10 distinct clusters per sequence on unenhanced T1- and Gd-EOB-DTPA-enhanced T1-weighted hepatobiliary phase (T1-Gd-EOB-DTPA-HBP), then on T1 in- and opposed-phase images. RLE and FF were quantified on identical sequences. Differences of these parameters between NASH and simple steatosis were evaluated with χ2- and t-tests, respectively. Linear regression and Random Forest classifier were performed to identify associations between histological NAFLD features, RLE, FF, and UDC patterns, and then determine predictors able to distinguish simple steatosis from NASH. ROC curves assessed diagnostic performance of UDC, RLE, and FF. Finally, we tested these parameters on 30 validation cohorts. RESULTS: For the derivation group, UDC-derived features from unenhanced and T1-Gd-EOB-DTPA-HBP, plus from T1 in- and opposed-phase, distinguished NASH from simple steatosis (p ≤ 0.001 and p = 0.02, respectively) with 85% and 80% accuracy, respectively, while RLE and FF distinguished NASH from simple steatosis (p ≤ 0.001 and p = 0.004, respectively), with 83% and 78% accuracy, respectively. On multivariate regression analysis, RLE and FF correlated only with fibrosis (p = 0.040) and steatosis (p ≤ 0.001), respectively. Conversely, UDC features, using Random Forest classifier predictors, correlated with all histologic NAFLD components. The validation group confirmed these results for both approaches. CONCLUSION: UDC, RLE, and FF could independently separate NASH from simple steatosis. UDC may predict all histologic NAFLD components. CLINICAL RELEVANCE STATEMENT: Using gadoxetic acid-enhanced MR, fat fraction (FF > 5%) can diagnose NAFLD, and relative liver enhancement can distinguish NASH from simple steatosis. Adding AI may let us non-invasively estimate the histologic components, i.e., fat, ballooning, inflammation, and fibrosis, the latter the main prognosticator. KEY POINTS: • Unsupervised deep clustering (UDC) and MR-based parameters (FF and RLE) could independently distinguish simple steatosis from NASH in the derivation group. • On multivariate analysis, RLE could predict only fibrosis, and FF could predict only steatosis; however, UDC could predict all histologic NAFLD components in the derivation group. • The validation cohort confirmed the findings for the derivation group.

Deep learning for predicting future lesion emergence in high-risk breast MRI screening: a feasibility study.

BACKGROUND: International societies have issued guidelines for high-risk breast cancer (BC) screening, recommending contrast-enhanced magnetic resonance imaging (CE-MRI) of the breast as a supplemental diagnostic tool. In our study, we tested the applicability of deep learning-based anomaly detection to identify anomalous changes in negative breast CE-MRI screens associated with future lesion emergence. METHODS: In this prospective study, we trained a generative adversarial network on dynamic CE-MRI of 33 high-risk women who participated in a screening program but did not develop BC. We defined an anomaly score as the deviation of an observed CE-MRI scan from the model of normal breast tissue variability. We evaluated the anomaly score's association with future lesion emergence on the level of local image patches (104,531 normal patches, 455 patches of future lesion location) and entire CE-MRI exams (21 normal, 20 with future lesion). Associations were analyzed by receiver operating characteristic (ROC) curves on the patch level and logistic regression on the examination level. RESULTS: The local anomaly score on image patches was a good predictor for future lesion emergence (area under the ROC curve 0.804). An exam-level summary score was significantly associated with the emergence of lesions at any location at a later time point (p = 0.045). CONCLUSIONS: Breast cancer lesions are associated with anomalous appearance changes in breast CE-MRI occurring before the lesion emerges in high-risk women. These early image signatures are detectable and may be a basis for adjusting individual BC risk and personalized screening. RELEVANCE STATEMENT: Anomalies in screening MRI preceding lesion emergence in women at high-risk of breast cancer may inform individualized screening and intervention strategies. KEY POINTS: • Breast lesions are associated with preceding anomalies in CE-MRI of high-risk women. • Deep learning-based anomaly detection can help to adjust risk assessment for future lesions. • An appearance anomaly score may be used for adjusting screening interval times.

Fetal brain tissue annotation and segmentation challenge results.

In-utero fetal MRI is emerging as an important tool in the diagnosis and analysis of the developing human brain. Automatic segmentation of the developing fetal brain is a vital step in the quantitative analysis of prenatal neurodevelopment both in the research and clinical context. However, manual segmentation of cerebral structures is time-consuming and prone to error and inter-observer variability. Therefore, we organized the Fetal Tissue Annotation (FeTA) Challenge in 2021 in order to encourage the development of automatic segmentation algorithms on an international level. The challenge utilized FeTA Dataset, an open dataset of fetal brain MRI reconstructions segmented into seven different tissues (external cerebrospinal fluid, gray matter, white matter, ventricles, cerebellum, brainstem, deep gray matter). 20 international teams participated in this challenge, submitting a total of 21 algorithms for evaluation. In this paper, we provide a detailed analysis of the results from both a technical and clinical perspective. All participants relied on deep learning methods, mainly U-Nets, with some variability present in the network architecture, optimization, and image pre- and post-processing. The majority of teams used existing medical imaging deep learning frameworks. The main differences between the submissions were the fine tuning done during training, and the specific pre- and post-processing steps performed. The challenge results showed that almost all submissions performed similarly. Four of the top five teams used ensemble learning methods. However, one team's algorithm performed significantly superior to the other submissions, and consisted of an asymmetrical U-Net network architecture. This paper provides a first of its kind benchmark for future automatic multi-tissue segmentation algorithms for the developing human brain in utero.

Evolution of cortical geometry and its link to function, behaviour and ecology.

Studies in comparative neuroanatomy and of the fossil record demonstrate the influence of socio-ecological niches on the morphology of the cerebral cortex, but have led to oftentimes conflicting theories about its evolution. Here, we study the relationship between the shape of the cerebral cortex and the topography of its function. We establish a joint geometric representation of the cerebral cortices of ninety species of extant Euarchontoglires, including commonly used experimental model organisms. We show that variability in surface geometry relates to species' ecology and behaviour, independent of overall brain size. Notably, ancestral shape reconstruction of the cortical surface and its change during evolution enables us to trace the evolutionary history of localised cortical expansions, modal segregation of brain function, and their association to behaviour and cognition. We find that individual cortical regions follow different sequences of area increase during evolutionary adaptations to dynamic socio-ecological niches. Anatomical correlates of this sequence of events are still observable in extant species, and relate to their current behaviour and ecology. We decompose the deep evolutionary history of the shape of the human cortical surface into spatially and temporally conscribed components with highly interpretable functional associations, highlighting the importance of considering the evolutionary history of cortical regions when studying their anatomy and function.

Fetal MRI based brain atlas analysis detects initial in utero effects of prenatal alcohol exposure.

Prenatal alcohol exposure (PAE) can change the normal trajectory of human fetal brain development and may lead to long-lasting neurodevelopmental changes in the form of fetal alcohol spectrum disorders. Currently, early prenatal patterns of alcohol-related central nervous system changes are unclear and it is unknown if small amounts of PAE may result in early detectable brain anomalies. This super-resolution fetal magnetic resonance imaging (MRI) study aimed to identify regional effects of PAE on human brain structure. Fetuses were prospectively assessed using atlas-based semi-automated 3-dimensional tissue segmentation based on 1.5 T and 3 T fetal brain MRI examinations. After expectant mothers completed anonymized PRAMS and TACE questionnaires for PAE, fetuses without gross macroscopic brain abnormalities were identified and analyzed. Linear mixed-effects modeling of regional brain volumes was conducted and multiple comparisons were corrected using the Benjamini-Hochberg procedure. In total, 500 pregnant women were recruited with 51 reporting gestational alcohol consumption. After excluding confounding comorbidities, 24 fetuses (26 observations) were identified with PAE and 52 age-matched controls without PAE were analyzed. Patients with PAE showed significantly larger volumes of the corpus callosum (P ≤ 0.001) and smaller volumes of the periventricular zone (P = 0.001). Even minor (1-3 standard drinks per week) PAE changed the neurodevelopmental trajectory.

Fetal temporal sulcus depth asymmetry has prognostic value for language development.

In most humans, the superior temporal sulcus (STS) shows a rightward depth asymmetry. This asymmetry can not only be observed in adults, but is already recognizable in the fetal brain. As the STS lies adjacent to brain areas important for language, STS depth asymmetry may represent an anatomical marker for language abilities. This study investigated the prognostic value of STS depth asymmetry in healthy fetuses for later language abilities, language localization, and language-related white matter tracts. Less right lateralization of the fetal STS depth was significantly associated with better verbal abilities, with fetal STS depth asymmetry explaining more than 40% of variance in verbal skills 6-13 years later. Furthermore, less right fetal STS depth asymmetry correlated with increased left language localization during childhood. We hypothesize that earlier and/or more localized fetal development of the left temporal cortex is accompanied by an earlier development of the left STS and is favorable for early language learning. If the findings of this pilot study hold true in larger samples of healthy children and in different clinical populations, fetal STS asymmetry has the potential to become a diagnostic biomarker of the maturity and integrity of neural correlates of language.

Fetal development of functional thalamocortical and cortico-cortical connectivity.

Measuring and understanding functional fetal brain development in utero is critical for the study of the developmental foundations of our cognitive abilities, possible early detection of disorders, and their prevention. Thalamocortical connections are an intricate component of shaping the cortical layout, but so far, only ex-vivo studies provide evidence of how axons enter the sub-plate and cortex during this highly dynamic phase. Evidence for normal in-utero development of the functional thalamocortical connectome in humans is missing. Here, we modeled fetal functional thalamocortical connectome development using in-utero functional magnetic resonance imaging in fetuses observed from 19th to 40th weeks of gestation (GW). We observed a peak increase of thalamocortical functional connectivity strength between 29th and 31st GW, right before axons establish synapses in the cortex. The cortico-cortical connectivity increases in a similar time window, and exhibits significant functional laterality in temporal-superior, -medial, and -inferior areas. Homologous regions exhibit overall similar mirrored connectivity profiles, but this similarity decreases during gestation giving way to a more diverse cortical interconnectedness. Our results complement the understanding of structural development of the human connectome and may serve as the basis for the investigation of disease and deviations from a normal developmental trajectory of connectivity development.