J. Ciaran Hutchinson

Imaging Invasion: Micro-CT imaging of adamantinomatous craniopharyngioma highlights cell type specific spatial relationships of tissue invasion

Tissue invasion and infiltration by brain tumours poses a clinical challenge, with destruction of structures leading to morbidity. We assessed whether micro-CT could be used to map tumour invasion in adamantinomatous craniopharyngioma (ACP), and whether it could delineate ACPs and their intrinsic components from surrounding tissue.Three anonymised archival frozen ACP samples were fixed, iodinated and imaged using a micro-CT scanner prior to the use of standard histological processing and immunohistochemical techniques.We demonstrate that micro-CT imaging can non-destructively give detailed 3D structural information of tumours in volumes with isotropic voxel sizes of 4–6 microns, which can be correlated with traditional histology and immunohistochemistry.Such information complements classical histology by facilitating virtual slicing of the tissue in any plane and providing unique detail of the three dimensional relationships of tissue compartments.

Early clinical applications for imaging at microscopic detail: microfocus computed tomography (micro-CT)

Microfocus CT (micro-CT) has traditionally been used in industry and preclinical studies, although it may find new applicability in the routine clinical setting. It can provide high-resolution three-dimensional digital imaging data sets to the same level of detail as microscopic examination without the need for tissue dissection. Micro-CT is already enabling non-invasive detailed internal assessment of various tissue specimens, particularly in breast imaging and early gestational fetal autopsy, not previously possible from more conventional modalities such as MRI or CT. In this review, we discuss the technical aspects behind micro-CT image acquisition, how early work with small animal studies have informed our knowledge of human disease and the imaging performed so far on human tissue specimens. We conclude with potential future clinical applications of this novel and emerging technique.

Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma

To assess the clinical relevance of transgenic and patient‐derived xenograft models of adamantinomatous craniopharyngioma (ACP) using serial magnetic resonance imaging (MRI) and high resolution post‐mortem microcomputed tomography (μ‐CT), with correlation with histology and human ACP imaging. The growth patterns and radiological features of tumors arising in Hesx1Cre/+;Ctnnb1lox(ex3)/+ transgenic mice, and of patient‐derived ACP xenografts implanted in the cerebral cortex, were monitored longitudinally in vivo with anatomical and functional MRI, and by ex vivo μ‐CT at study end. Pathological correlates with hematoxylin and eosin stained sections were investigated. Early enlargement and heterogeneity of Hesx1Cre/+;Ctnnb1lox(ex3)/+ mouse pituitaries was evident at initial imaging at 8 weeks, which was followed by enlargement of a solid tumor, and development of cysts and hemorrhage. Tumors demonstrated MRI features that recapitulated those of human ACP, specifically, T1‐weighted signal enhancement in the solid tumor component following Gd‐DTPA administration, and in some animals, hyperintense cysts on FLAIR and T1‐weighted images. Ex vivo μ‐CT correlated with MRI findings and identified smaller cysts, which were confirmed by histology. Characteristic histological features, including wet keratin and calcification, were visible on μ‐CT and verified by histological sections of patient‐derived ACP xenografts. The Hesx1Cre/+;Ctnnb1lox(ex3)/+ transgenic mouse model and cerebral patient‐derived ACP xenografts recapitulate a number of the key radiological features of the human disease and provide promising foundations for in vivo trials of novel therapeutics for the treatment of these tumors.

Learning effect on perinatal post‐mortem magnetic resonance imaging reporting: single reporter diagnostic accuracy of 200 cases

The objective of the study is to compare diagnostic accuracy of perinatal post‐mortem magnetic resonance (PMMR) imaging against conventional autopsy, when reported by a single‐blinded observer for all organ systems following a period of initial experience.

Imaging the human placental microcirculation with micro-focus computed tomography: Optimisation of tissue preparation and image acquisition

Micro-CT provides 3D volume imaging with spatial resolution at the micrometre scale. We investigated the optimal human placenta tissue preparation (contrast agent, perfusion pressure, perfusion location and perfusion vessel) and imaging (energy, target material, exposure time and frames) parameters. Microfil (Flow Tech, Carver, MA) produced better fill than Barium sulphate (84.1%(±11.5%)vs70.4%(±18.02%) p = 0.01). Perfusion via umbilical artery produced better fill than via chorionic vessels (83.8%(±17.7%)vs78.0%(±21.9%), p < 0.05), or via umbilical vein (83.8%(±16.4%)vs69.8%(±20.3%), p < 0.01). Imaging at 50 keV with a molybdenum target produced the best contrast to noise ratio. We propose this method to enable quantification and comparison of the human fetoplacental vascular tree.

Three-Dimensional Imaging-Based Web Application for Predicting Tracheal Tube Depth in Preterm Neonates.

Background: Positioning a tracheal tube (TT) to the correct depth in preterm infants is challenging. Currently, there is no reliable single-predictor model for neonates applicable to the whole range of size or age. Objective: In this study, we used post-mortem magnetic resonance imaging (PMMRI) of preterm infants to measure tracheal dimensions and to develop a clinical guide for TT positioning. Methods: We measured tracheal length (TL) and tracheal diameter (TD) in a cohort of normal neonates and foetuses that underwent PMMRI (cause of death unexplained). The distance between the lips and the mid-tracheal point, i.e., the mid-tracheal length (mid-TL), and the TD measurement were obtained. We produced univariate prediction models of mid-TL and TD, using gestational age (GA), foot length (FL), crown-rump length (CRL) and body weight (BW) as potential predictors, as well as multiple prediction models for mid-TL. Results: Tracheal measurements were performed in 117 cases, with a mean GA of 28.8 weeks (range 14-42 weeks). The best linear association was between mid-TL and FL (mid-TL = FL × 0.914 + 1.859; R2 = 0.94), but was improved by multivariate regression models. We developed a prediction tool using only GA and BW (R2 = 0.92), and all four predictors (GA, BW, FL and CRL; R2 = 0.94) which is now available as a web-based application via the Internet. Conclusion: Post-mortem imaging data provide estimates of TT insertion depth. Our prediction tool based on age and BW can be used at the bedside and is ready to be tested in clinical practice.

Development and Autopsy Assessment of the Fetal Head and Face

Embryonic development of the head and face is a complex process occurring during the first trimester, involving interactions between components from all three germ layers, between neural tube formation and associated head and facial development and between multiple branchial/pharyngeal arch components. For these reasons, numerous abnormalities may occur depending on the site, timing and severity of any defects in these processes. However, the general types and mechanisms of such anomalies can be reasonably grouped together, and this chapter aims to provide a brief overview of the major components of facial development in association with clinically significant fetal abnormalities. In addition, the chapter will briefly describe the approach to investigation of such abnormalities at autopsy and major associated features. For those interested, there are excellent and highly detailed accounts available of these processes from an embryological perspective, documenting the mechanisms of cellular interactions during these processes and with experimental evidence for the developmental origins of the various components, which are beyond the scope of this chapter [7, 12, 16, 21].

The Role of Cross-Sectional Imaging in the Investigation of Childhood Deaths

As autopsy practices continue to evolve, new imaging techniques are introduced. Imaging has long played a part in the investigation of suspicious childhood deaths, largely because of the nature of occult fractures being only identifiable through skeletal survey radiographs. Cross-sectional imaging is now more readily available in most institutions, including post mortem multi-detector computed tomography (PMCT) and magnetic resonance imaging (PMMR). Whilst the majority of the evidence-base for their use is likely to come from a non-forensic setting, the added value of PMCT and PMMR to forensic investigations will become clear over time. This chapter is divided into four sections: 1. Paediatric autopsy practice, the nature of childhood deaths and why post mortem imaging is increasingly appealing 2. Imaging modalities and their advantages and disadvantages 3. Use of cross-sectional imaging in specific circumstances (trauma, non-accidental injury, hanging, etc.) 4. Additional benefits of cross-sectional imaging (post mortem interval, modeling)