Mathematical/computational challenges in creating deformable and probabilistic atlases of the human brain

Striking variations in brain structure, especially in the gyral patterns of the human cortex, present fundamental challenges in human brain mapping. Probabilistic brain atlases, which encode information on structural and functional variability in large human populations, are powerful research tools with broad applications. Knowledge-based imaging algorithms can also leverage atlased information on anatomic variation. Applications include automated image labeling, pathology detection in individuals or groups, and investigating how regional anatomy is altered in disease, and with age, gender, handedness and other clinical or genetic factors. In this report, we illustrate some of the mathematical challenges involved in constructing population-based brain atlases. A disease-specific atlas is constructed to represent the human brain in Alzheimer's disease (AD). Specialized strategies are developed for population-based averaging of anatomy. Sets of high-dimensional elastic mappings, based on the principles of continuum mechanics, reconfigure the anatomy of a large number of subjects in an anatomic image database. These mappings generate a local encoding of anatomic variability and are used to create a crisp anatomical image template with highly resolved structures in their mean spatial location. Specialized approaches are also developed to average cortical topography. Since cortical patterns are altered in a variety of diseases, gyral pattern matching is used to encode the magnitude and principal directions of local cortical variation. In the resulting cortical templates, subtle features emerge. Regional asymmetries appear that are not apparent in individual anatomies. Population-based maps of cortical variation reveal a mosaic of variability patterns that segregate sharply according to functional specialization and cytoarchitectonic boundaries.     

Perioperative optimisation of fluid management improves outcome

Mortality from high-risk surgery is close to 10% (20% with emergency). Poor outcome is linked to tissue hypoperfusion. Optimising fluid therapy has a good pathophysiological basis related to microvascular flow to the tissues and the risk of multiple organ failure. Metaanalysis showed the higher the risk of surgery the greater the benefit of fluid and flow optimisation. A direct technique (blood pressure is indirect) to manage fluid therapy measuring tissues perfusions has not yet fulfilled criteria (easiness, accuracy, less invasiveness). At present pulmonary artery catheter with continuous output measurement is the choice. The aim of the study is to assess the impact of fluid management to increase blood flow in high-risk surgical patient.     

Role of n-3 fatty acids in prevention of disease complications in patients with HIV.

Hypertriglyceridemia and insulin resistance have been seen in patients with HIV. Beneficial effects of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported for these conditions. One study of n-3 fatty acid supplementation in patients with HIV reported a decrease in serum triglyceride levels. These marine fatty acids appear to be working at a number of sites to achieve an improvement in lipid metabolism and insulin sensitivity. There is disagreement about the amount of n-3 fatty acids needed to achieve different effects and about the optimal ratio of dietary n-6 and n-3 fatty acids.     

A UK multi‐centre pilot study of speech and swallowing outcomes following head and neck cancer

Speech and swallowing are important components of health‐related quality of life following head and neck cancer treatment. The aim of this study was to demonstrate the value of prospective multi‐centre evaluation by Speech and Language Therapists and to compare health‐related quality of life with speech and swallowing impairments. The University of Washington Head and Neck questionnaire version 4 (UW‐QOL) and Therapy Outcome Measures (TOM) were rated before and 6 months after cancer treatment in 95 patients from 12 centres. There was deterioration in TOM scores at 6 months. Pretreatment UW‐QOL swallowing was ranked equal first, with speech fourth. At 6 months speech was first and swallowing second. There were positive correlations between UW‐QOL swallowing and TOM dysphagia and between UW‐QOL speech and TOM laryngectomy, voice, phonology and dysarthria disorders. Both outcome measures are suitable for routine practice. Adaptation of TOM scales for use with head and neck cancer patients may improve sensitivity, validity and therapist compliance.     

The development of the emetic reflex in the house musk shrew, Suncus murinus

The emetic (retching and vomiting) reflex is an important component of the body's defence system against accidentally ingested toxins and emesis is also a common symptom of disease and a side-effect of a number of pharmacological therapies. The development of the reflex has been the subject of few systematic studies. The aim of this study was to characterise the development of the emetic reflex in Suncus murinus (the house musk shrew) using emetic stimuli acting via three different afferent pathways: motion via the vestibular system, pyrogallol via abdominal vagal afferents and resiniferatoxin (a capsaicin analog) via the brainstem. The emetic reflex was not present to any stimulus prior to postnatal day 10 but the onset of the response to motion lagged behind that to the other stimuli in not being present until postnatal day 15. Body weight was not a determinant of the presence of the reflex. It is proposed that the delayed presence of the emetic reflex in Suncus makes it an ideal species in which to investigate factors regulating its development.     

Interactions between spatial attention and global/local feature selection: an ERP study

The present study examined the interaction between spatial attention and global/local feature processing of visual hierarchical stimuli. Event-related brain potentials (ERPs) were recorded from subjects who detected global or local targets at attended locations while ignoring those at unattended locations. Spatial attention produced enhanced occipital P1 and N1 waves in both global and local conditions. Selection of local features enhanced posterior P1, N1 and N2 waves relative to selection of global features. However, the modulations of the P1 and N2 by global/local feature selection were stronger when spatial attention was directed to the left than the right visual fields. The results suggest neurophysiological bases for interactions between spatial attention and hierarchical analysis at multiple stages of visual processing.     

Morphometric analysis and fine structure of the vestibular epithelium of aged C57BL/6NNia mice

The vestibular organs of young and very old C57BL/6NNia (B6) mice were compared by light and electron microscopy. Hair cell density decreased an average of 14% in the utricle, 19% in the saccule and posterior crista, 23% in the horizontal crista, and 24% in the anterior crista. Hair cell size remained the same throughout the mouse's life span as did the ratio of Type I to Type II hair cells. The most apparent sign of advanced age was dense inclusions found in sensory and supporting cells. Although small inclusions were present at five weeks, by 29 months, additional, larger forms appeared. An unusual melanin-like form was characteristic of old Type I hair cells. Synaptic morphology and synaptic bodies were well preserved even in very old B6 mice. Elongated bars were common in Type I hair cells and spheroid synaptic bodies were the most common form in Type II hair cells. Large clusters of synaptic bodies occurring in both young and old mice were seen only in Type I hair cells. Although the B6 strain suffers from genetically determined early cochlear degeneration, it does not experience early degeneration of the peripheral vestibular organs.     

Placental villous surface area of light-for-dates infants at term

The placental villous surface area and ratios of villous surface area to body weight, length and head circumference were determined in 40 light-for-dates infants born at term. When infants were categorised by length, head circumference and ponderal index, the short infants and infants with small heads had a mean villous surface area similar to that of their peers of normal length and head circumference. However, wasted infants, with a low ponderal index, had both an absolutely and relatively reduced mean villous surface area when compared to non-wasted infants. It is concluded that not all light-for-dates infants, but only those that are wasted at birth, have quantitative placental inadequacy.