In recent years, clinical neuroscience has steadily transitioned from standardized, population-based reference values toward a more individualized and patient-specific approach. This paradigm shift is particularly relevant for neuroimaging, where quantitative volumetric assessment increasingly informs diagnostic, prognostic, and therapeutic decision-making [8,15,16]. Within this context, the PCF represents a uniquely constrained anatomical compartment in which even subtle volumetric imbalances may have disproportionate clinical consequences [17, 18]. Importantly, infarct volumes were comparable across age groups and between sexes, with no statistically significant differences observed. This finding suggests that lesion size did not act as a confounding factor in the assessment of age- and sex-related differences in posterior cranial fossa volumetry.
The present study, comprising a large cohort of 1,280 adult subjects of different ages and sex, provides comprehensive normative data on age- and sex-related volumetric changes of the PCF and its contents. We observed a marked age-related reduction in cerebellar volume across the studied age range (p < .001), accompanied by a smaller but statistically significant decrease in total PCF volume. These findings indicate that aging is associated with a progressive reduction of infratentorial neural tissue, most prominently affecting the cerebellum. Age-related cerebellar atrophy has been extensively investigated in healthy populations [19]. In contrast to previous studies focusing primarily on parenchymal volume loss, our analysis highlights the resulting changes in posterior fossa reserve capacity. From a clinical perspective, the available cerebrospinal fluid space within the posterior cranial fossa may be as important as neural tissue volume itself when evaluating tolerance to acute space-occupying lesions.
Although total PCF volume demonstrated a small but statistically significant decline with increasing age, this reduction was markedly less pronounced than the age-related decrease in cerebellar volume. As a result, PCF-CSFv – the “reserve” spaces - showed a progressive increase across the adult lifespan. From a clinical perspective, even relatively small absolute differences in infratentorial reserve volume may be highly relevant. An additional reserve of approximately ~ 9.5 cm³, as observed between the youngest and oldest age groups, may critically influence the tolerance to space-occupying lesions within the confined PCF.
Cranial growth is completed in early adulthood, subtle age-related changes of the cranial base have been described, such changes may result in a modest reduction of the intracranial compartment without alterations of the external skull dimensions [20, 21].
Importantly, persistent sex-related volumetric differences were observed throughout adulthood. Males exhibited larger PCF, cerebellar, and brainstem volumes compared to females, both within individual age groups and when analyzing the cohort as a whole. This stable sexual dimorphism highlights the limitations of uniform reference values and underscores the necessity of sex-specific normative frameworks, particularly when evaluating infratentorial pathologies.
From a clinical perspective, volumetric relationships within the PCF are of critical importance. The classical Monro-Kellie doctrine conceptualizes the intracranial compartment as a closed system maintaining equilibrium among brain tissue, cerebrospinal fluid, and blood volume [22]. However, this global concept may insufficiently reflect regional infratentorial dynamics. For example, Kuramatsu et al. demonstrated that in patients with spontaneous cerebellar hemorrhage exceeding 15 cm³—within a cohort with a median age of 68.8 years—surgical intervention was associated with improved clinical outcomes [23]. In a similar context, Won et al. demonstrated that in patients with acute cerebellar infarction, an infarct volume of 35 cm³ represented a critical threshold associated with neurological deterioration and the need for surgical intervention, in a cohort with a median age of 68 years [9]. These findings further support the concept that absolute lesion volume plays an important role in clinical decision-making for infratentorial pathology. When interpreted in light of our results, however, such volume-based thresholds should be viewed within the broader framework of individual PCF anatomy.
Our data indicate substantial age-dependent differences in PCF volume and the “reserve” space, suggesting that individual tolerance to space-occupying lesions may vary considerably. Consequently, patients aged 60 and 80 years may differ markedly in their infratentorial volumetric reserve and compensatory capacity, even when lesion volumes are identical. This observation challenges the notion of universally applicable “critical volumes” and highlights the need for a more individualized approach. Our findings suggest that age-related expansion of infratentorial cerebrospinal fluid spaces may provide partial compensation for neural tissue loss; however, this compensatory reserve appears to be limited and highly individual.
The use of neuroimaging volumetric analysis in this study reflects the increasing feasibility of incorporating quantitative measurements into routine clinical practice [16]. Advances in automated and semi-automated segmentation software now enable reliable, reproducible, and near–real-time assessment of posterior cranial fossa structures, thereby facilitating the translation of volumetric research findings into clinically applicable metrics [24]. In the era of personalized medicine, such quantitative approaches are likely to play a central role in tailoring diagnostic thresholds and therapeutic strategies to individual patients.
Future studies using harmonized imaging protocols should compare alternative volumetric approaches, including segmentation-, atlas-, and voxel-based techniques. Such work may enable the derivation of group-averaged volumetric measures and the generation of representative images illustrating structural changes across the cohort.
In conclusion, this study demonstrates that aging and sex significantly influence the volumetric anatomy of the PCF and its contents. The observed imbalance between declining neural tissue volumes and expanding cerebrospinal fluid spaces highlights the importance of individualized infratentorial volumetric assessment. As neuroimaging continues to move toward personalized medicine, quantitative evaluation of PCF anatomy may become an essential component in the assessment and management of infratentorial pathology.
LimitationsSeveral limitations should be acknowledged. First, the retrospective and cross-sectional design may have introduced selection bias and does not permit assessment of individual longitudinal changes. Second, the multicenter cohort included MRI and CT examinations acquired using different scanners and clinical protocols, which may have introduced measurement variability despite the use of standardized segmentation methods. Third, the study population consisted of patients with cerebellar stroke and did not include a healthy control group; therefore, the findings should be interpreted as reference data for a vascular population and may not be directly generalizable to healthy individuals. Intracranial volume was not consistently available, precluding normalization for individual head size. In addition, measurements were performed in native anatomical space without MNI-based normalization, and the heterogeneous multimodal dataset did not allow standardized voxel-based morphometry. Finally, intracranial pressure measurements and detailed clinical outcome data were unavailable, preventing direct assessment of the physiological and prognostic relevance of the observed volumetric differences.
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