Comparison of Three Methods for the Estimation of Pineal Gland Volume Using Magnetic Resonance Imaging

Pineal gland is a very important neuroendocrine organ with many physiological functions such as regulating circadian rhythm. Radiologically, the pineal gland volume is clinically important because it is usually difficult to distinguish small pineal tumors via magnetic resonance imaging (MRI). Although many studies have estimated the pineal gland volume using different techniques, to the best of our knowledge, there has so far been no stereological work done on this subject. The objective of the current paper was to determine the pineal gland volume using stereological methods and by the region of interest (ROI) on MRI. In this paper, the pineal gland volumes were calculated in a total of 62 subjects (36 females, 26 males) who were free of any pineal lesions or tumors. The mean ± SD pineal gland volumes of the point-counting, planimetry, and ROI groups were 99.55 ± 51.34, 102.69 ± 40.39, and 104.33 ± 40.45 mm3, respectively. No significant difference was found among the methods of calculating pineal gland volume (P > 0.05). From these results, it can be concluded that each technique is an unbiased, efficient, and reliable method, ideally suitable for in vivo examination of MRI data for pineal gland volume estimation

The effect of realistic geometries on the susceptibility-weighted MR signal in white matter

Purpose: To investigate the effect of realistic microstructural geometry on the susceptibility-weighted magnetic resonance (MR) signal in white matter (WM), with application to demyelination. Methods: Previous work has modeled susceptibility-weighted signals under the assumption that axons are cylindrical. In this work, we explore the implications of this assumption by considering the effect of more realistic geometries. A three-compartment WM model incorporating relevant properties based on literature was used to predict the MR signal. Myelinated axons were modeled with several cross-sectional geometries of increasing realism: nested circles, warped/elliptical circles and measured axonal geometries from electron micrographs. Signal simulations from the different microstructural geometries were compared to measured signals from a Cuprizone mouse model with varying degrees of demyelination. Results: Results from simulation suggest that axonal geometry affects the MR signal. Predictions with realistic models were significantly different compared to circular models under the same microstructural tissue properties, for simulations with and without diffusion. Conclusion: The geometry of axons affects the MR signal significantly. Literature estimates of myelin susceptibility, which are based on fitting biophysical models to the MR signal, are likely to be biased by the assumed geometry, as will any derived microstructural properties.Comment: Accepted March 4 2017, in publication at Magnetic Resonance in Medicin

A monte carlo study of restricted diffusion: Implications for diffusion MRI of prostate cancer

Purpose: Diffusion MRI is frequently used to assess prostate cancer. The prostate consists of cellular tissue surrounding fluid filled ducts. Here, the diffusion properties of the ductal fluid alone were studied. Monte Carlo simulations were used to investigate ductal residence times to determine whether ducts can be regarded as forming a separate compartment and whether ductal radius could determine the ADC of the ductal fluid. Methods: Random walks were simulated in cavities. Average residence times were estimated for permeable cavities. Signal reductions resulting from application of a Stejskal-Tanner pulse sequence were calculated in impermeable cavities. Simulations were repeated for cavities of different radii and different diffusion times. Results: Residence times are at least comparable with diffusion times even in relatively high grade tumours. ADCs asymptotically approach theoretical limiting values. At large radii and short diffusion times, ADCs are similar to free diffusion. At small radii and long diffusion times, ADCs are reduced towards zero, and kurtosis approaches a value of -1.2. Conclusions: Restricted diffusion in cavities of similar sizes to prostate ducts may reduce ductal ADCs. This may contribute to reductions in total ADC seen in prostate cancer

Variation in Brain Morphology of Intertidal Gobies: A Comparison of Methodologies Used to Quantitatively Assess Brain Volumes in Fish

When correlating brain size and structure with behavioural and environmental characteristics, a range of techniques can be utilised. This study used gobiid fishes to quantitatively compare brain volumes obtained via three different methods; these included the commonly used techniques of histology and approximating brain volume to an idealised ellipsoid, and the recently established technique of X-ray micro-computed tomography (micro-CT). It was found that all three methods differed significantly from one another in their volume estimates for most brain lobes. The ellipsoid method was prone to over- or under-estimation of lobe size, histology caused shrinkage in the telencephalon, and although micro-CT methods generated the most reliable results, they were also the most expensive. Despite these differences, all methods depicted quantitatively similar relationships among the four different species for each brain lobe. Thus, all methods support the same conclusions that fishes inhabiting rock pool and sandy habitats have different patterns of brain organisation. In particular, fishes from spatially complex rock pool habitats were found to have larger telencephalons, while those from simple homogenous sandy shores had a larger optic tectum. Where possible we recommend that micro-CT be used in brain volume analyses, as it allows for measurements without destruction of the brain and fast identification and quantification of individual brain lobes, and minimises many of the biases resulting from the histology and ellipsoid methods

Evaluating fibre orientation dispersion in white matter: comparison of diffusion MRI, histology and polarized light imaging

Diffusion MRI is an exquisitely sensitive probe of tissue microstructure, and is currently the only non-invasive measure of the brain’s fibre architecture. As this technique becomes more sophisticated and microstructurally informative, there is increasing value in comparing diffusion MRI with microscopic imaging in the same tissue samples. This study compared estimates of fibre orientation dispersion in white matter derived from diffusion MRI to reference measures of dispersion obtained from polarized light imaging and histology. Three post-mortem brain specimens were scanned with diffusion MRI and analyzed with a two-compartment dispersion model. The specimens were then sectioned for microscopy, including polarized light imaging estimates of fibre orientation and histological quantitative estimates of myelin and astrocytes. Dispersion estimates were correlated on region – and voxel-wise levels in the corpus callosum, the centrum semiovale and the corticospinal tract. The region-wise analysis yielded correlation coefficients of r=0.79 for the diffusion MRI and histology comparison, while r=0.60 was reported for the comparison with polarized light imaging. In the corpus callosum, we observed a pattern of higher dispersion at the midline compared to its lateral aspects. This pattern was present in all modalities and the dispersion profiles from microscopy and diffusion MRI were highly correlated. The astrocytes appeared to have minor contribution to dispersion observed with diffusion MRI. These results demonstrate that fibre orientation dispersion estimates from diffusion MRI represents the tissue architecture well. Dispersion models might be improved by more faithfully incorporating an informed mapping based on microscopy data

Effect of skull type on the relative size of cerebral cortex and lateral ventricles in dogs

Volume measurements of the brain are of interest in the diagnosis of brain pathology. This is particularly so in the investigation hydrocephalus and canine cognitive dysfunction (CCD), both of which result in thinning of the cerebral cortex and enlarged ventricles. Volume assessment can be made using computed tomography or more usually magnetic resonance imaging (MRI). There is, however, some uncertainty in the interpretation of such volume data due to the great variation in skull size and shape seen in dog. In this retrospective study, we examined normal MRI images from 63 dogs <6 years of age. We used a continuous variable, the cranial index (CrI) to indicate skull shape and compared it with MRI volume measurements derived using Cavalieri’s principle. We found a negative correlation between CrI and the ratio of cortical to ventricular volume. Breeds with a high CrI (large laterolateral compared to rostrocaudal cranial cavity dimension) had a smaller ratio of cortical to ventricular volume (low C:V ratio) than breeds with lower CrI skull types. It is important to consider this effect of skull shape on the relative volume estimates of the cerebral cortex and ventricles when trying to establish if pathology is present

Development of a novel MRI technique for imaging the ischaemic penumbra in experimental stroke

In Scotland, stroke is the third most common cause of death behind heart disease and cancer. However, most strokes are not fatal and can cause severe disability, with one third of survivors still functionally dependent after one year. The advent of recombinant tissue plasminogen activator (rT-PA) as a thrombolytic modality revolutionised the treatment for ischaemic stroke, providing a treatment aimed to promptly restore nutritional blood flow to the ischaemic penumbra, a transient tissue state which is amenable to salvage. Crucially, patient ineligibility from a multitude of factors (including the narrow time window for benefit and the risk of intracranial haemorrhage) means that fewer than 10% of all stroke patients are thrombolysed. Positive identification of penumbra is not employed in the current intravenous rT-PA administration strategy, which is instead based on two main prerequisites: stroke patients in whom intracerebral haemorrhage has been excluded with non-contrast computed tomography (CT) and who also present within 4.5 hours of symptom onset. The technical impracticalities and limited availability of the gold standard penumbral imaging modality, multitracer 15O positron emission tomography (PET), and the lack of standardised thresholds to identify penumbra using non-contrast CT have hindered the development and inclusion of routine brain imaging in the management of acute stroke patients. An alternative research tool which may potentially be used in clinical practice is magnetic resonance imaging (MRI) which defines penumbra on the basis of diffusion-perfusion (DWI/PWI) mismatch. However, this provides an imprecise measure of penumbra and fails to identify tissue viability. Current PET-derived definitions of penumbra use metabolic indices such as oxygen extraction fraction (OEF) and the cerebral metabolic rate of oxygen (CMRO2), which are not fully incorporated into MR definitions. This thesis presents an alternative MRI method for identifying the metabolic penumbra in a rodent model of focal cerebral ischaemia. This utilises an MRI sequence similar to that used in functional MRI (fMRI) techniques, and uses 100% oxygen inhalation as a biotracer to detect penumbral tissue. Specifically, by using a blood oxygen level dependent (BOLD) T2*-weighted sequence in which changes in the deoxyhaemoglobin:oxyhaemoglobin ratio are detected - in conjunction with a transient hyperoxic challenge (Oxygen Challenge (OC) paradigm: 5 minutes breathing air followed by 5 minutes breathing 100% oxygen) - penumbral tissue can be distinguished from adjacent ischaemic core and benign oligaemia (Santosh et al, 2008). Changes in CBF, cerebral blood volume (CBV), tissue oxygenation, and oxidative metabolism can all influence the T2* signal (Ramsay et al, 1993; Corfield et al, 2001), so it was important to evaluate the possibility that factors other than tissue metabolism were influencing the signal change during OC. An initial study was performed which showed that baseline CBF did not influence T2* signal response to OC, whilst a greater increase in the percentage change in arterial oxygen saturation following OC caused an increased magnitude in T2* percentage signal change in contralateral tissue and penumbra, but not in ischaemic core. Arterial oxygen levels (PaO2) affect the magnitude of the T2* signal change to OC, with lower baseline PaO2 levels amplifying the T2* signal response in metabolically active regions, implying that careful control of physiological variables may optimise the T2*OC technique. The first validation study used [14C] 2-deoxyglucose autoradiography to determine the metabolic status of penumbra defined by T2*OC MRI. The results confirmed that glucose metabolism in the T2*OC-defined penumbra was comparable to contralateral values, whereas markedly different levels of glucose metabolism were evident in the ADC-derived ischaemic core and an adjacent region of increased 2DG phosphorylation. From this, it was concluded that metabolic information could be yielded from the ischaemic brain that may improve delineation of the penumbra using the OC technique. As penumbral tissue must fulfil the fundamental criteria of being potentially salvageable and responsive to therapy, the consequences of reperfusion on the T2*OC-defined penumbra was tested. This study confirmed that T2*OC-defined penumbra displayed a T2* signal change significantly higher than contralateral tissue during ischaemia which subsequently returned to contralateral levels following reperfusion and did not progress to infarction when assessed at day 7 following stroke. Finally, the spatiotemporal characteristics of the T2*OC-defined penumbra were investigated and compared with DWI/PWI mismatch-defined penumbra. Serial scanning demonstrated that T2*OC penumbra behaved in a similar manner to tissue defined by traditional mismatch criterion. The spatial location and tissue volumes of penumbra were similar with both methods, showing that, in animals where mismatch tissue volume reduced over time, T2*OC penumbra reduced similarly, and in animals where mismatch volume remained static over time, T2*OC-defined penumbra behaved similarly. Additionally, an interesting finding arose in the latter study which showed that ischaemic damage continues to progress beyond 4 hours following permanent MCAO, which may be relevant to the calculation of ADC and CBF thresholds used in defining DWI/PWI mismatch. Collectively, the preclinical data support the potential of T2*OC to discriminate tissue compartments in acute stroke based on metabolic status which thereby provides an alternative and improved means of defining the ischaemic penumbra