Introduction
Since gaining recognition in post-mortem practice in the early 1990s [
1], the role and contribution of post-mortem imaging techniques in the investigation of cause of death continue to be extensively evaluated and the concept of minimally invasive autopsies (MIA) continues to gain importance. The usefulness of both post-mortem CT (PMCT), its extension post-mortem CT angiography (PMCTA) and post-mortem MRI (PMMR) as adjuncts in the context of forensic autopsies has been established, and these techniques are increasingly being implemented around the world [
2,
3]. PMCT clearly visualises the skeletal system, whilst PMCTA, introduced approximately 10 years ago, delivers an ideal visualisation of the vascular system [
4‐
8]. Finally, PMMR offers excellent soft-tissue contrast which would otherwise be unachievable. In recent years, developments in post-mortem imaging have increasingly focused on addressing recognised diagnostic weaknesses, especially with respect to suspected natural deaths. More specifically, the need to define the role of post-mortem imaging in the assessment of sudden cardiac death (SCD) was underlined in a review of the current state of post-mortem imaging regarding cardiovascular pathologies [
9]. The post-mortem evaluation of ischemic heart disease (IHD), the most common underlying cause of SCD, involves examination of the coronary arteries, for stenosis and occlusions as well as examination of the myocardium for signs of ischemia [
10]. A combined MIA protocol (CT, MRI and biopsy) used to detect cardiac causes of death was compared to conventional autopsy (CA), resulting in the conclusion that MIA is still insufficient in this area [
11]. The need to improve upon this insufficiency currently fuels the development of post-mortem imaging techniques. For example, PMCTA successfully visualises the morphology of coronary arteries to rule out significant stenosis and identify the presence of occlusions [
12], whilst PMMR enhances the ability to visualise contrast in soft tissue, with promising performance in the detection of myocardial infarction [
13‐
16]. However, challenges related to infrastructure, the complexity of PMMR (e.g. temperature-dependent contrast) and the influence of post-mortem changes have led to a slower advancement of this technique [
4].
Most recently, initial experience has been gained with post-mortem MR angiography (PMMRA) [
4]. The technical feasibility of PMMRA was demonstrated using a small cohort; however, sedimentation problems negatively affected image quality [
4,
17]. A PMMRA acquisition protocol for ex situ hearts using a lipophilic contrast agent mixture (paraffin oil and Angiofil®) can also be found in the literature [
18]; however, to our knowledge, a systematic evaluation of potentially suitable perfusates and imaging protocols in the context of PMMRA has not yet been undertaken.
A complete filling of targeted vessels, specifically of the coronary arteries, is required to enable reliable radiological assessment of the vasculature in the heart. Due to the delicate state and increased permeability of the vascular wall in cadavers, careful consideration of the factors affecting the behaviour of liquids in the vascular system (e.g. nature, viscosity) [
4] is required. In current PMCTA applications, aqueous, hygroscopic and lipophilic solutions can be found; however, hygroscopic and lipophilic liquids are often recommended due to their reduced extravasation over time into surrounding tissue [
4]. For polyethylene glycol (e.g. PEG200, hygroscopic) solutions, increased viscosity (∼55 mPa · s measured at 20 °C) was found to positively influence the clarity of the vascular image [
19]. For paraffin oil (lipophilic), a viscosity of approximately 31 mPa · s (measured at “room temperature”) was considered appropriate, due to its non-observation in capillaries [
20]. Furthermore, the viscosity of a given liquid is strongly dependent on its temperature [
21]. This was confirmed by examination of different PEG200 solutions, highlighting the need to adapt viscosity to local temperature conditions, including cadaver temperature [
22]. A detailed characterisation of the temperature dependence of multiple perfusate viscosities is nevertheless lacking in the literature, meaning that an accurate knowledge of in-cadaver viscosity of liquids used in PMCTA and potentially of interest for PMMRA is not currently available. This study responds to this deficiency and additionally seeks to model dynamic viscosity of potential perfusates over a forensically relevant temperature range.
In addition to a complete filling of the relevant region of the vascular system, knowledge of the attainable contrast in MR images is also necessary when evaluating liquids as potential PMMRA perfusates. Such contrast is determined by the intrinsic properties (e.g., relaxation times) of the administered perfusate and surrounding tissue, as well as by the imaging sequence applied. Studies examining post-mortem tissue and phantoms have already demonstrated that relaxation times are temperature-dependent [
23‐
28], and additional studies implementing PMMR have highlighted the importance of this dependence [
13,
16]. The current study provides fundamental information regarding the temperature dependence of the relaxation times (T
1, T
2) for a number of potential perfusates. Furthermore, it is possible to approximate the contrast attainable for a selected MR imaging sequence using numerical simulations. To better understand the complex behaviour of different substances in MRI, simulations repeatedly solve the Bloch equations [
29] under ideal conditions. Such simulations exploit information intrinsic to the investigated substances, as well as sequence parameters, and are important tools in the development and optimisation of MRI protocols, prior to acquiring experimental MR images.
The main objective of this study was to evaluate the suitability of different liquids for inclusion in a targeted PMMRA protocol. To effectively evaluate such liquids, this work sought to investigate temperature variations for a paraffinum liquidum + Angiofil® (6 %) solution in perfused cadavers, to characterise selected liquids in terms of their temperature-dependent dynamic viscosity and intrinsic MR properties (T
1, T
2) and finally to simulate possible contrast achievable against post-mortem tissue using experimentally obtained relaxation times (perfusates) and literature values (cadaveric tissue [
27]) using a radiofrequency (RF)-spoiled gradient echo (GRE) sequence.
Conclusion
This work evaluated the suitability of different liquids for inclusion in a targeted PMMRA protocol. Two preferred liquids, paraffin oil and a solution of paraffin oil + Angiofil® (6 %), were identified. The quadratic model approximating in-cadaver temperature of paraffinum liquidum + Angiofil® (6 %) based on cadaver temperature at the time of external examination may also be applied more generally for other liquids with similar physical properties. The characterised dynamic viscosities and intrinsic MR properties (T
1, T
2), as well as their temperature-dependent models, were used to evaluate the suitability of liquids for use as perfusates in a targeted approach to PMMRA, leading to the identification of the two preferred liquids. Simulation of a RF-spoiled GRE sequence revealed the potential contrast achievable between these preferred liquids and relevant cadaveric tissues based on the modelled temperature dependence of relaxation times found in [
27]. Interestingly, differences in the temperature dependence of relaxation properties for post-mortem tissues [
27] and the preferred perfusates led to better contrast in simulations at lower temperatures.
The approach described in this work provides important information for optimising sequence parameters, especially at institutes where scanner access for forensic cases is limited. The study contributes fundamental knowledge of potential perfusates as well as a preliminary exploration of MR sequencing parameters to aid in the systematic development of PMMRA, with the ultimate goal of further improving minimally invasive post-mortem diagnosis of sudden cardiac death.