Autopsy and Photon Counting Computed Tomography to Evaluate Thromboses Related to Central Venous Catheters

Purpose and specific objective The aim of the current project (PHOTO CAT) is to evaluate the prevalence of subclinical thromboses related to central venous catheters (CVCs) using a novel high-resolution photon-counting computed tomography (CT) scan and to evaluate the performance of the photon-counting CT compared to clinical autopsy.

Scientific questions

• Can the photon-counting CT diagnose subclinical CVK-related thromboses detected at later autopsy?
• How common are CVC-related thromboses in autopsies of deceased people with existing CVC?
• How does the performance of the photon counting DT compare to clinical autopsy?
• How common are CVC-related thromboses in a cohort that does photon-counting DT for various reasons and has a CVC?
• Can imaging be improved by adjustments to the DT protocol?
• Can an ultrasound scan on living patients diagnose subclinical CVK-related thrombosis detected by photon-counting CT?

Background CVCs are essential in modern healthcare and have a wide range of applications. They enable direct access to the central bloodstream and are used, among other things, to administer medicines, nutrition and to monitor blood circulation. Unfortunately, they are associated with a variety of complications, including thrombosis. Studies report thrombosis incidences between 5 - 30% in living patients. When the CVC is introduced into the blood vessel, a number of physiological defense systems are initiated. Inflammation and clotting are activated, leading to the formation of a fibrin stocking around the catheter. This can then develop into a catheter-related thrombosis, which in turn can have serious consequences for the patient, such as pulmonary embolism or infection.

Photon-counting DT is the new generation of DT. What distinguishes this from the traditional one is that the radiation through the body is detected with a new type of detector that measures each X-ray, which provides significantly greater precision and resolution for a given radiation dose compared to traditional CT. This is particularly valuable in imaging diagnostics that rely on detailed morphology such as high-resolution CT of lungs. In order to achieve its full potential with as little radiation dose and contrast volume as possible with preserved image resolution, the design of protocols for the photon-counting CT needs to be optimized.

Autopsy studies on CVC-related thrombosis and vascular changes are few. In a case series from 1994, changes in the vessel wall were examined macroscopically and biofilms were assessed with electron microscopy. The presence of fibrin stocking on the surface of all CVCs (n = 72), and wall-mounted thrombosis was reported in 38% of cases. In another autopsy study, Forauer et al. demonstrated severe CVC-related vascular changes that included intima damage with infiltration of media by inflammatory cells and varying degrees of adherent thrombus. Wichmann et al. published data showing a 38% prevalence of macroscopic catheter-related thrombosis in 61 human autopsies. In a recently published autopsy study, we showed that 12 out of 12 cases had CVC-related mural thrombosis at autopsy, with most being located in the distal part of the CVC (Rockholt et al.).

There are also a number of clinical studies that have investigated how common CVC-related thrombosis is using ultrasound. In a well-designed prospective study, 16.9% of ICU patients had subclinical CVK-related thrombosis. The problem with the ultrasound method is that the distal part of the CVC is difficult to visualize with ultrasound, which means that the thrombosis incidence risks being underestimated.

Material and method In an attempt to investigate how common subclinical CVK-related thrombosis, the current studies, include photon-counting CT, were designed.

In substudy 1, photon counting CT is used to examine deceased intensive care patients referred for autopsy on clinical indication, with CVC in-situ. The CT will be focused on the vein with the CVC but a full body examination will also be done . Both examination results will be compared with the clinical autopsy conducted after the examinations. This first part of PHOTO CAT includes Scientific questions 1-3.

In sub-study 2, living patients with CVC who are referred for CT scan without contrast, will be eligable for inclusion. After consent, the study will be carried out with photon counting CT in two phases. First, the examination for which the patient was referred, will be performed. In the second phase, a targeted examination is performed for research purposes of the vein with the CVC. Within 12 hours before or after the CT scan, it is planned to perform an ultrasound scan of the vein where the CVC is located. The aim is to evaluate the performance of ultrasound examination in detecting CVC-related thrombosis, compared to photon-counting CT. Sub-study 2 of PHOTO CAT includes Questions 4-6.

Analysis of data and statistics No one has previously reported photon-counting CT to detect CVC-related thromboses. Therefore, the current exploratory study is planned. The results may form the basis for sample size calculation in future studies.

Significance In patients with CVC, subclinical CVC-related thromboses are very common. These seem to cause surprisingly few clinical problems. However, it should be noted that several of the actual symptoms that CVC-related thrombosis can cause may go unnoticed or misinterpreted as symptoms of the disease that caused the patient's to need of a CVC. It is important to know the true incidence of subclinical CVC-related thrombosis in order to evaluate the risk-benefit of central venous access compared to alternatives (peripheral venous access, midline, PICCLINE, porth-a-cath), and in the development of new less thrombogenic CVC materials.

Substudy 1

Inclusion criteria

• Diseased patients with an indwelling central venous catheter and a clinical indication for autopsy
• Informed and signed consent from next of kind

Exclusion criteria

• None

Substudy 2 Inclusion Criteria

• Living patients with an indwelling central venous catheter who are referred to a CT scan without iv contrast
• Informed and signed consent from the patient

Exclusion criteria

• GFR <15 mL/min/1.73 m2