Biology subjects

Herigstad, M.

Publications and source records attributed to Herigstad, M..

3 recordsLinked to original sources

bioRxiv2017

Imaging seminiferous tubules - a 9.4T MRI mouse model

Fertility problems affect many couples. Research into male fertility commonly uses mouse models due to their availability and similar spermatogenesis to humans. A common target is the seminiferous tubules, the site of spermatozoa production, typically studied using biopsies and histological analysis. High-field Magnetic Resonance (MR) may offer a non-invasive alternative to investigate testicular function in infertility models. Here, we assess seminiferous tubules structure in sacrificed mice to determine the usefulness of MR compared to histology. Twelve mice (11 aged 35-57 days, one >9 months) were sacrificed and MR imaged at 9.4T with a Rapid Acquisition with Relaxation Enhancement sequence. Testes were scanned in situ for all mice, and excised in a subset of mice (n=4). A second subset of mice (n=4) had their testes selected for histological analysis. Seminiferous tubule diameter was measured manually from MRI and histology images. Custom image analysis scripts were created for the automated segmentation of seminiferous tubules and calculation of tissue volumes. All ex vivo and in situ images of testes exhibited clear outlines of seminiferous tubules. Ratio of total testis volume to volume of seminiferous tubules did not differ significantly between ex vivo and in situ measurements, and were similar in mature and younger mice. Both total testis volume and seminiferous tubule volume were larger in the mature animal. While histological slices trended towards larger average seminiferous tubules diameter than MRI images, we found no significant differences between MRI and histological measurements. High-field MRI can be used in a mouse model to assess testicular structure in situ. All volumetric measurements compared favourably with histological data. In situ scans also clearly showed identifiable extra-testicular tissues, such as epididymis and prostate tissues. The potential to image tissues associated with sperm maturation as well as spermatogenesis emphasises how MR could be a useful technique in mouse models of fertility, however further work is required to optimize tissue segmentation and validate this method for use in longitudinal studies. This type of measurement could be extended to human fertility studies in the future.

physiology↗

bioRxiv2017

Low-Level Carbon Monoxide Exposure Affects BOLD FMRI

Blood Oxygen Level Dependent (BOLD) FMRI is a common technique for measuring brain activation that could be affected by low-level carbon monoxide (CO) exposure from e.g. smoking. This study aimed to probe the vulnerability of BOLD FMRI to CO and determine whether it constitutes a significant confound in neuroimaging and clinical trials. Low-level (6ppm exhaled) CO effects on BOLD signal were assessed in 12 healthy never-smokers on two separate experimental days (CO and air control). FMRI tasks were breath-holds (hypercapnia), visual stimulation and fingertapping. CO significantly dampened global BOLD FMRI signal during hypercapnia and visual cortex activation during visual stimulation. During fingertapping, CO reduced visual cortex activation but increased premotor cortex activation. Behavioural and physiological measures remained unchanged. We conclude that BOLD FMRI is vulnerable to CO, possibly through baseline increases in CBF, and suggest exercising caution when imaging populations exposed to elevated CO levels, e.g. with high smoking prevalence.

neuroscience↗

bioRxiv2017

Treating the lungs via the brain: Mechanisms underpinning improvements in breathlessness with pulmonary rehabilitation.

BackgroundBreathlessness in chronic obstructive pulmonary disease (COPD) is often discordant with airway pathophysiology (\"over-perception\"). Pulmonary rehabilitation has profound effects upon breathlessness, without influencing lung function. Learned associations can influence brain mechanisms of sensory perception. We therefore hypothesised that improvements in breathlessness with pulmonary rehabilitation may be explained by changing neural representations of learned associations, reducing \"over-perception\".\n\nMethodsIn 31 patients with COPD, we tested how pulmonary rehabilitation altered the relationship between brain activity during learned associations with a word-cue task (using functional magnetic resonance imaging), clinical, and psychological measures of breathlessness.\n\nResultsImprovements in breathlessness and breathlessness-anxiety correlated with reductions in word-cue related activity in the insula and anterior cingulate cortex (ACC) (breathlessness), and increased activations in attention regulation and motor networks (breathlessness-anxiety). Greater baseline (pre-rehabilitation) activity in the insula, ACC and prefrontal cortex correlated with the magnitude of improvement in breathlessness and breathlessness anxiety.\n\nConclusionsPulmonary rehabilitation reduces the influence of learned associations upon neural processes that generate breathlessness. Patients with stronger word-cue related activity at baseline benefitted more from pulmonary rehabilitation. These findings highlight the importance of targeting learned associations within treatments for COPD, demonstrating how neuroimaging may contribute to patient stratification and more successful personalised therapy.

neuroscience↗