Figure - available from: Brain Structure and Function
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a The fornix (fx) is a large C-shaped white matter structure shown here at the level of the anterior commissure. b The fornix (fx) is a large C-shaped white matter structure. Note that at the level of the hypothalamus the fx has formed two columns that will connect to the mamillary bodies (MB). c The fornix (fx) is a large C-shaped white matter structure. Note the disappearance of the fornical columns posterior to the mamillary bodies
Source publication
The growing interest in the human subcortex is accompanied by an increasing number of parcellation procedures to identify deep brain structures in magnetic resonance imaging (MRI) contrasts. Manual procedures continue to form the gold standard for parcellating brain structures and is used for the validation of automated approaches. Performing manua...
Citations
... • Cold room (4 • C; postfixation). the vertebral arteries, this does not negatively affect the quality of the brain fixation (see below). It would be very difficult to meet the need of preserving the neck anatomy as much as possible if the two vertebral arteries were to be identified and cannulated, as a broader and deeper dissection of the base of the neck-or even the cutting off of the head-would be required (Alkemade et al., 2022). ...
... The intracarotid perfusion of the brain has been reliably used to obtain MRI images that can be co-registered onto histology sections. This approach (nowadays widely used by us and others) provides the best anatomical correspondence to MRI images, to conduct several different determinations of brain parameters (Iglesias et al., 2018;Wisse et al., 2021a;Yushkevich et al., 2021;Alkemade et al., 2022). Previous work by our laboratory and others approximated histology and MRI images, not belonging to the same subjects, resulting in only a proxy for anatomical annotations of MRI images (Insausti et al., 1998;Franko et al., 2014;Delgado-Gonzalez et al., 2015). ...
... However, our method provides a consistent quality of fixation and, in our experience, uniform immunohistochemistry using, for example, anti-Tau AT8 stain along 8-10 cm of tissue blocks, corresponding to the whole rostrocaudal extent of a complete human temporal lobe, in an extensive series of cases [Yushkevich et al. (2021), 21 cases]. This highlights the consistency of the method in terms of collecting larger series than in other studies [e.g., Bian et al. (2016), three cases; Beaujoin et al. (2018), one case; Alkemade et al. (2022), two cases]. The same holds true for its applicability to intracellular filling and electron microscopy. ...
We present a method for human brain fixation based on simultaneous perfusion of 4% paraformaldehyde through carotids after a flush with saline. The left carotid cannula is used to perfuse the body with 10% formalin, to allow further use of the body for anatomical research or teaching. The aim of our method is to develop a vascular fixation protocol for the human brain, by adapting protocols that are commonly used in experimental animal studies. We show that a variety of histological procedures can be carried out (cyto- and myeloarchitectonics, histochemistry, immunohistochemistry, intracellular cell injection, and electron microscopy). In addition, ex vivo, ex situ high-resolution MRI (9.4T) can be obtained in the same specimens. This procedure resulted in similar morphological features to those obtained by intravascular perfusion in experimental animals, provided that the postmortem interval was under 10 h for several of the techniques used and under 4 h in the case of intracellular injections and electron microscopy. The use of intravascular fixation of the brain inside the skull provides a fixed whole human brain, perfectly fitted to the skull, with negligible deformation compared to conventional techniques. Given this characteristic of ex vivo, in situ fixation, this procedure can probably be considered the most suitable one available for ex vivo MRI scans of the brain. We describe the compatibility of the method proposed for intravascular fixation of the human brain and fixation of the donor's body for anatomical purposes. Thus, body donor programs can provide human brain tissue, while the remainder of the body can also be fixed for anatomical studies. Therefore, this method of human brain fixation through the carotid system optimizes the procurement of human brain tissue, allowing a greater understanding of human neurological diseases, while benefiting anatomy departments by making the remainder of the body available for teaching purposes.
The human subcortex comprises hundreds of unique structures. Subcortical functioning is crucial for behavior, and disrupted function is observed in common neurodegenerative diseases. Despite their importance, human subcortical structures continue to be difficult to study in vivo. Here we provide a detailed account of 17 prominent subcortical structures and ventricles, describing their approximate iron and myelin contents, morphometry, and their age-related changes across the normal adult lifespan. The results provide compelling insights into the heterogeneity and intricate age-related alterations of these structures. They also show that the locations of many structures shift across the lifespan, which is of direct relevance for the use of standard magnetic resonance imaging atlases. The results further our understanding of subcortical morphometry and neuroimaging properties, and of normal aging processes which ultimately can improve our understanding of neurodegeneration.
Uncertainties
concerning anatomy and function of cortico-subcortical projections have arisen during the recent years. A clear distinction between cortico-subthalamic (hyperdirect) and cortico-tegmental projections (superolateral medial forebrain bundle, slMFB) so far is elusive. Deep Brain Stimulation (DBS) of the slMFB (for major depression, MD and obsessive compulsive disorders, OCD) has on the one hand been interpreted as actually involving limbic (prefrontal) hyperdirect pathways. On the other hand slMFB’s stimulation region in the mesencephalic ventral tegmentum is said to impact on other structures too, going beyond the antidepressant (or anti OCD) efficacy of sole modulation of the cortico-tegmental reward-associated pathways. We have here used a normative diffusion MRT template (HCP, n = 80) for long-range tractography and augmented this dataset with ex-vivo high resolution data (n = 1) in a stochastic brain space. We compared this data with histological information and used the high resolution ex-vivo data set to scrutinize the mesencephalic tegmentum for small fiber pathways present. Our work resolves an existing ambiguity between slMFB and prefrontal hyperdirect pathways which—for the first time—are described as co-existent. DBS of the slMFB does not appear to modulate prefrontal hyperdirect cortico-subthalamic but rather cortico-tegmental projections. Smaller fiber structures in the target region—as far as they can be discerned—appear not to be involved in slMFB DBS. Our work enfeebles previous anatomical criticism and strengthens the position of the slMFB DBS target for its use in MD and OCD.
