Project – MRI-Based Assessment of Hippocampal Volume in Adults and Its Anatomical Significance: A Study of MRI Scans at LUTH

CHAPTER ONE

INTRODUCTION

1.1 Background to the Study

The hippocampus is a paired, elongated structure located within the medial temporal lobe of each cerebral hemisphere and forms an important component of the limbic system. Anatomically, it is closely associated with the dentate gyrus, subiculum and related parahippocampal structures, while functionally it plays an important role in learning, memory, spatial navigation and the formation and consolidation of new memories. Because of its strategic anatomical location and functional connections with cortical and subcortical regions, structural alterations of the hippocampus can have important neurological and cognitive consequences. Modern neuroimaging has therefore made the hippocampus an important structure for anatomical assessment in both healthy individuals and patients with neurological disorders (Duvernoy, 2005; Strange et al., 2014).

Magnetic Resonance Imaging (MRI) provides a non-invasive method for visualising the hippocampus in vivo and allows quantitative assessment of its anatomical characteristics. Unlike conventional radiography and computed tomography, MRI provides excellent soft-tissue contrast, making it particularly suitable for evaluating brain structures such as the hippocampus. High-resolution T1-weighted MRI sequences can be used to identify the boundaries of the hippocampal formation and estimate its volume through manual tracing, semi-automated segmentation or automated segmentation techniques. Quantitative hippocampal volumetry has consequently become an important method for investigating structural variation in the human brain (Jack et al., 1997; Pruessner et al., 2000; Wenger et al., 2014). The reliability of such measurements, however, depends on image quality, segmentation methodology, scanner characteristics and the anatomical criteria used to define the hippocampal boundaries (Wenger et al., 2014).

Hippocampal volume is not uniform across individuals and may vary according to factors such as age, sex, total intracranial volume and laterality. Large normative MRI datasets have demonstrated that age and sex are important predictors of subcortical brain volumes, while the volume of the hippocampus may also differ between the right and left sides. A study involving 302 healthy adults reported a mean hippocampal volume of approximately 3.81 cm³ and found significantly larger mean hippocampal volume in males than females, as well as a significant difference between right and left hippocampal volumes. These findings demonstrate the importance of establishing appropriate reference values when interpreting hippocampal volume in individual subjects rather than assuming that one absolute value represents normality for every adult (Cheon et al., 2019; Potvin et al., 2017).

Age is another important factor in hippocampal morphometry. Although the degree and pattern of age-related hippocampal change remain subjects of investigation, longitudinal and cross-sectional MRI research has demonstrated that hippocampal volume generally declines with advancing age. A systematic review and meta-analysis involving 28 longitudinal studies and more than 3,400 participants reported an overall hippocampal atrophy rate of approximately 0.85% per year, with higher rates among older age groups. Research examining hippocampal subfields has further shown that different parts of the hippocampus may demonstrate different degrees of vulnerability to ageing, suggesting that total hippocampal volume may not fully capture the complexity of age-related anatomical change (Fraser et al., 2015; Pereira et al., 2014).

The anatomical significance of hippocampal volume extends beyond normal ageing because hippocampal atrophy is an established structural feature in several neurological and neuropsychiatric conditions. In Alzheimer’s disease, for example, hippocampal volume reduction has been consistently associated with disease-related neurodegeneration and cognitive impairment. MRI studies have demonstrated that hippocampal atrophy can occur in Alzheimer’s disease beyond the changes associated with normal ageing, with particularly prominent involvement of regions corresponding to the CA1 sector and other hippocampal areas. Quantitative hippocampal measurements can therefore provide useful anatomical information for differentiating normal structural variation from pathological changes when interpreted together with clinical and cognitive findings (Jack et al., 1997; Frisoni et al., 2008).

Hippocampal volumetry is also relevant to the assessment of temporal lobe epilepsy and mesial temporal sclerosis. Structural MRI is routinely used to identify abnormalities of the hippocampal formation in individuals with suspected temporal lobe epilepsy, and hippocampal volume asymmetry can provide an important anatomical clue when hippocampal sclerosis is present. However, accurate assessment requires an understanding of normal hippocampal size and left-right variation because physiological asymmetry can occur in healthy adults. Consequently, normative volumetric information can strengthen the interpretation of hippocampal abnormalities and improve the anatomical basis for clinical decision-making (Jack et al., 1997; Pruessner et al., 2000; Strange et al., 2014).

The methodological approach used in MRI-based hippocampal volumetry is itself an important anatomical consideration. Manual tracing remains a widely used reference method, but it is time-consuming and can be influenced by differences between observers and by the anatomical criteria used during segmentation. Automated approaches such as FreeSurfer have increased the feasibility of analysing large numbers of scans, although differences between manual and automated methods can produce systematic differences in estimated hippocampal volume. Wenger et al. (2014), for example, demonstrated high repeatability for both manual and automated measurements but also identified systematic differences between the methods, emphasizing the need for methodological consistency when comparing hippocampal measurements. Similarly, large lifespan studies have shown that MRI sequence characteristics can influence estimates of hippocampal subfield volumes (Wenger et al., 2014; Billot et al., 2021).

In the Nigerian context, MRI-based assessment of hippocampal anatomy is particularly relevant because locally generated neuroanatomical reference information can complement findings from populations in Europe, North America and other regions. Lagos University Teaching Hospital (LUTH) is a major tertiary healthcare and research institution with a Department of Radiodiagnosis that provides imaging services involving the central nervous system and conducts research activities. The availability of MRI examinations within such a clinical environment provides an opportunity for anatomical research based on routinely acquired adult brain scans, subject to appropriate ethical approval, inclusion criteria and protection of patient confidentiality. A study of hippocampal volume using MRI scans at LUTH can therefore contribute to the development of locally relevant anatomical information and provide a basis for understanding variation in hippocampal volume among adults in the Nigerian clinical population.

1.2 Statement of the Problem

The hippocampus is a structurally complex brain region whose volume varies between individuals and is influenced by several biological and methodological factors. Despite the increasing use of MRI in neurological practice and research, interpretation of an individual’s hippocampal volume requires reliable knowledge of what constitutes expected anatomical variation. Without appropriate reference information, a relatively small or large hippocampus may be difficult to distinguish from normal individual variation, particularly when factors such as age, sex, intracranial volume and hemispheric differences are not adequately considered (Potvin et al., 2017; Cheon et al., 2019).

A major problem is that hippocampal volume changes with ageing, but the pattern of change is not necessarily uniform across the entire hippocampal formation. Longitudinal evidence indicates that hippocampal atrophy becomes more pronounced with advancing age, while MRI studies of hippocampal subfields demonstrate different levels of susceptibility to age-related structural change. Consequently, using a single volumetric reference value for all adults may result in inappropriate interpretation of hippocampal size. There is therefore a need for studies that examine hippocampal volume in relation to adult age and establish anatomical patterns that can assist in distinguishing expected age-related variation from potentially abnormal reduction in volume (Fraser et al., 2015; Pereira et al., 2014).

Another problem concerns the clinical significance of reduced hippocampal volume. Hippocampal atrophy has been associated with conditions such as Alzheimer’s disease, temporal lobe epilepsy and other disorders involving memory and cognition. However, the interpretation of hippocampal volume requires comparison with appropriate anatomical standards because a measurement that appears abnormal without consideration of age, sex, laterality and measurement methodology may lead to misleading conclusions. Studies have shown that normative hippocampal volumetric data can improve the interpretation of structural MRI findings, but normative datasets are not necessarily transferable without consideration of population and technical differences (Jack et al., 1997; Frisoni et al., 2008; Cheon et al., 2019).

Furthermore, there is a need for more locally relevant MRI-based anatomical information on hippocampal volume among adults undergoing brain imaging in Nigeria. Much of the established literature on normative hippocampal volume has been generated from non-African populations and from imaging centres using different scanners, acquisition protocols and segmentation procedures. LUTH provides a suitable clinical environment for investigating adult brain anatomy through MRI, and its Department of Radiodiagnosis includes central nervous system imaging among its services and research activities. A systematic assessment of hippocampal volume from appropriately selected adult MRI scans at LUTH can therefore help address the paucity of locally applicable anatomical data and provide information that may be useful for anatomical research, radiological interpretation and future clinical studies in the Nigerian population.

1.3 Aim of the Study

The aim of this study is to assess hippocampal volume in adults using Magnetic Resonance Imaging (MRI) scans at Lagos University Teaching Hospital (LUTH) and determine its anatomical significance.

1.4 Objectives of the Study

The specific objectives are to:

1. Determine the mean right and left hippocampal volumes of adults using MRI scans at Lagos University Teaching Hospital.
2. Assess the relationship between hippocampal volume and selected demographic variables, particularly age and sex, among the adults studied.
3. Determine the degree of right-left hippocampal volume asymmetry among the adult MRI scans examined.
4. Evaluate the anatomical and potential clinical significance of the observed hippocampal volumetric patterns in relation to normal adult brain anatomy and MRI-based assessment.

1.5 Research Questions

The following research questions will guide the study:

1. What are the mean right and left hippocampal volumes of adults assessed using MRI scans at LUTH?
2. What relationship exists between hippocampal volume and selected demographic variables, particularly age and sex?
3. What degree of right-left hippocampal volume asymmetry exists among the adults studied?
4. What is the anatomical and potential clinical significance of the observed hippocampal volumetric patterns?

1.6 Research Hypothesis

Null Hypothesis (H₀): There is no statistically significant relationship between hippocampal volume and selected demographic characteristics, particularly age and sex, among adults whose MRI scans are assessed at Lagos University Teaching Hospital.

1.7 Significance of the Study

The study will be significant to anatomists and neuroanatomy educators because it will provide quantitative information on the size and laterality of the hippocampus in adults. The findings can supplement conventional descriptions of hippocampal anatomy by providing measurable MRI-based information about an important structure of the medial temporal lobe.

The study will also be useful to radiologists and medical imaging professionals because hippocampal volumetry provides quantitative information that can complement visual assessment of brain MRI. Establishing the distribution of hippocampal volumes in the study population may assist in understanding normal anatomical variation and may provide a foundation for future studies involving patients with suspected hippocampal pathology.

The findings may be relevant to neurologists, neurosurgeons and other clinicians involved in disorders affecting memory, cognition and the medial temporal lobe. Hippocampal volume has been investigated extensively in conditions such as Alzheimer’s disease and temporal lobe epilepsy, and locally relevant anatomical information may support future clinical research into these conditions (Jack et al., 1997; Frisoni et al., 2008).

The study will further be useful to researchers in neuroscience, radiology and anatomy by providing data that can be compared with findings from other populations. Such comparisons may help identify similarities and differences in hippocampal volume associated with age, sex, laterality and methodological factors.

Finally, the study will contribute to Nigerian anatomical and radiological literature by generating MRI-based information from an adult population undergoing imaging at LUTH. The findings may serve as preliminary reference data for subsequent larger multicentre studies designed to establish normative hippocampal volumes for Nigerian adults.

1.8 Scope of the Study

The study will focus on the MRI-based assessment of hippocampal volume in adults whose eligible MRI brain scans are available at Lagos University Teaching Hospital. The study will concentrate on the right and left hippocampi and will assess their volumes using an appropriate and consistently applied MRI segmentation or volumetric measurement protocol.

The study will examine hippocampal volume in relation to selected demographic characteristics, particularly age and sex, and will assess right-left hippocampal asymmetry. The study will also discuss the anatomical and potential clinical significance of the observed volumetric patterns.

The study will be restricted to adult MRI scans that satisfy the predetermined inclusion and exclusion criteria. Scans with severe motion artefacts, major structural abnormalities that interfere with hippocampal delineation, incomplete demographic information or inadequate image quality for reliable volumetric assessment will be excluded as appropriate.

1.9 Operational Definition of Terms

Hippocampus: A paired curved structure located in the medial temporal lobe and forming an important component of the brain’s memory-related neural circuitry.

Hippocampal Volume: The three-dimensional amount of anatomical space occupied by the hippocampus, usually expressed in cubic millimetres or cubic centimetres and measured from MRI images.

Hippocampal Volumetry: The quantitative process of determining the volume of the hippocampus from medical imaging data.

Magnetic Resonance Imaging (MRI): A non-invasive imaging technique that uses magnetic fields and radiofrequency signals to generate detailed images of internal body structures, including the brain.

MRI Scan: A series of magnetic resonance images acquired according to a specified imaging protocol.

Adult: An individual who has reached adulthood according to the age criterion established for the study.

Hippocampal Asymmetry: The difference in volume between the right and left hippocampi.

Right Hippocampus: The hippocampal formation located in the medial temporal region of the right cerebral hemisphere.

Left Hippocampus: The hippocampal formation located in the medial temporal region of the left cerebral hemisphere.

Hippocampal Atrophy: A reduction in hippocampal volume relative to an appropriate reference or expected anatomical value.

Anatomical Significance: The relevance of the observed hippocampal size, shape, laterality and volumetric variation to normal human neuroanatomy and interpretation of structural brain imaging.

Normative Data: Quantitative anatomical measurements obtained from individuals considered to represent a reference or healthy population.

Segmentation: The process of identifying and delineating the boundaries of the hippocampus from surrounding brain structures on MRI images in order to calculate its volume.

Project – MRI-Based Assessment of Hippocampal Volume in Adults and Its Anatomical Significance: A Study of MRI Scans at LUTH