Risk factors for atherosclerotic and medial arterial calcification of the intracranial internal carotid artery

_Background and aims:_ Calcifications of the intracranial internal carotid artery (iICA) are an important risk factor for stroke. The calcifications can occur both in the intimal and medial layer of the vascular wall. The aim of this study is to assess whether medial calcification in the iICA is differently related to risk factors for cardiovascular disease, compared to intimal calcification. _Methods:_ Unenhanced thin slice computed tomography (CT) scans from 1132 patients from the Dutch acute stroke study cohort were assessed for dominant localization of calcification (medial or intimal) by one of three observers based on established methodology. Associations between known cardiovascular risk factors (age, gender, body mass index, pulse pressure, eGFR, smoking, hypertension, diabetes mellitus, hyperlipidemia, previous vascular disease, and family history) and the dominant localization of calcifications were assessed via logistic regression analysis. _Results:_ In the 1132 patients (57% males, mean age 67.4 years [SD 13.8]), dominant intimal calcification was present in 30.9% and dominant medial calcification in 46.9%. In 10.5%, no calcification was seen. Age, pulse pressure and family history were risk factors for both types of calcification. Multivariably adjusted risk factors for dominant intimal calcification only were smoking (OR 2.09 [CI 1.27–3.44]) and hypertension (OR 2.09 [CI 1.29–3.40]) and for dominant medial calcification diabetes mellitus (OR 2.39 [CI 1.11–5.14]) and previous vascular disease (OR 2.20 [CI 1.30–3.75]). _Conclusions:_ Risk factors are differently related to the dominant localizations of calcifications, a finding that supports the hypothesis that the intimal and medial calcification represents a distinct etiology

The amount of calcifications in pseudoxanthoma elasticum patients is underestimated in computed tomographic imaging; a post-mortem correlation of histological and computed tomographic findings in two cases

OBJECTIVES: Pseudoxanthoma elasticum (PXE) is a rare genetic disorder, characterised by elastic fibre degeneration and calcifications in multiple organ systems. Computed tomography (CT) imaging is a potential method to monitor disease progression in PXE patients; however, this method has not been validated. The aim of this study was to correlate histological and computed tomographic findings in PXE patients to investigate the ability of CT scanning to detect these alterations. METHODS: Post mortem total body CT scans were obtained from two PXE patients (a 69-year-old male and 77-year-old female). Autopsy was performed, and 38 tissue samples of the first and 45 tissue samples of the second patient were extensively investigated histologically. The findings were compared with the CT scans. RESULTS: Degenerated and calcified elastic fibres and calcifications were histologically found in the skin, subcutaneous fat, heart, arteries and pleura and around the oesophagus. On CT imaging only the intradermal alterations of the skin and the larger vascular calcifications were detected. The smaller PXE-related abnormalities were not visible on CT. CONCLUSIONS: With CT imaging vascular calcifications and skin alterations can be monitored in PXE patients. However, many of the subtle PXE-related abnormalities found in other organ systems during the autopsy were not visualised by CT scans. Furthermore, we extended the current knowledge on the disease location of PXE with subcutaneous, oesophageal and pleural lesions. TEACHING POINTS: • CT can be used to monitor gross vascular calcifications in PXE patients. • Many subtle PXE-related abnormalities are not visualised by CT scans. • PXE-related alterations can also be found in oesophagus, pleura and subcutaneous fat

The amount of calcifications in pseudoxanthoma elasticum patients is underestimated in computed tomographic imaging; a post-mortem correlation of histological and computed tomographic findings in two cases

Objectives: Pseudoxanthoma elasticum (PXE) is a rare genetic disorder, characterised by elastic fibre degeneration and calcifications in multiple organ systems. Computed tomography (CT) imaging is a potential method to monitor disease progression in PXE patients; however, this method has not been validated. The aim of this study was to correlate histological and computed tomographic findings in PXE patients to investigate the ability of CT scanning to detect these alterations. Methods: Post mortem total body CT scans were obtained from two PXE patients (a 69-year-old male and 77-year-old female). Autopsy was performed, and 38 tissue samples of the first and 45 tissue samples of the second patient were extensively investigated histologically. The findings were compared with the CT scans. Results: Degenerated and calcified elastic fibres and calcifications were histologically found in the skin, subcutaneous fat, heart, arteries and pleura and around the oesophagus. On CT imaging only the intradermal alterations of the skin and the larger vascular calcifications were detected. The smaller PXE-related abnormalities were not visible on CT. Conclusions: With CT imaging vascular calcifications and skin alterations can be monitored in PXE patients. However, many of the subtle PXE-related abnormalities found in other organ systems during the autopsy were not visualised by CT scans. Furthermore, we extended the current knowledge on the disease location of PXE with subcutaneous, oesophageal and pleural lesions. Teaching Points: • CT can be used to monitor gross vascular calcifications in PXE patients. • Many subtle PXE-related abnormalities are not visualised by CT scans. • PXE-related alterations can also be found in oesophagus, pleura and subcutaneous fat

Radiography and Computed Tomography Detection of Intimal and Medial Calcifications in Leg Arteries in Comparison to Histology

Calcifications are common in the tunica intima and tunica media of leg arteries. There is growing interest in medial arterial calcifications, as they may be modifiable with treatment. We aimed to investigate radiography and computed tomography (CT) for the detection and characterization of both types of arterial calcification in leg arteries in relation to histology. In a postmortem study we therefore investigated 24 popliteal and 24 tibial arteries. The reference standard was presence of arterial calcification and the dominance of intimal or medial calcification on histology. Radiographs and CT scans were scored for presence of calcification and for dominant intimal or medial pattern based on prespecified criteria (annularity, thickness, continuity). Both radiography and CT detected 87% of histologically proven calcifications but missed mild calcifications in 13%. When only the arteries with detected calcifications were included, a moderate agreement was observed on intimal/medial location of calcifications between histology and radiography (correct in 19/24 arteries (79%); Kappa 0.58) or CT (correct in 33/46 arterial segments (72%); Kappa 0.48). With both modalities there was a slight tendency to classify intimal calcifications as being located in the media and to miss media calcification. Our study demonstrates the potential and limitations of both radiography and CT to detect and classify arterial calcifications in leg arteries

The amount of calcifications in pseudoxanthoma elasticum patients is underestimated in computed tomographic imaging; a post-mortem correlation of histological and computed tomographic findings in two cases

OBJECTIVES: Pseudoxanthoma elasticum (PXE) is a rare genetic disorder, characterised by elastic fibre degeneration and calcifications in multiple organ systems. Computed tomography (CT) imaging is a potential method to monitor disease progression in PXE patients; however, this method has not been validated. The aim of this study was to correlate histological and computed tomographic findings in PXE patients to investigate the ability of CT scanning to detect these alterations. METHODS: Post mortem total body CT scans were obtained from two PXE patients (a 69-year-old male and 77-year-old female). Autopsy was performed, and 38 tissue samples of the first and 45 tissue samples of the second patient were extensively investigated histologically. The findings were compared with the CT scans. RESULTS: Degenerated and calcified elastic fibres and calcifications were histologically found in the skin, subcutaneous fat, heart, arteries and pleura and around the oesophagus. On CT imaging only the intradermal alterations of the skin and the larger vascular calcifications were detected. The smaller PXE-related abnormalities were not visible on CT. CONCLUSIONS: With CT imaging vascular calcifications and skin alterations can be monitored in PXE patients. However, many of the subtle PXE-related abnormalities found in other organ systems during the autopsy were not visualised by CT scans. Furthermore, we extended the current knowledge on the disease location of PXE with subcutaneous, oesophageal and pleural lesions. TEACHING POINTS: • CT can be used to monitor gross vascular calcifications in PXE patients. • Many subtle PXE-related abnormalities are not visualised by CT scans. • PXE-related alterations can also be found in oesophagus, pleura and subcutaneous fat

Predominance of Nonatherosclerotic Internal Elastic Lamina Calcification in the Intracranial Internal Carotid Artery

BACKGROUND AND PURPOSE—: Calcification of the intracranial internal carotid artery (iICA) is an independent risk factor for stroke. These calcifications are generally seen as manifestation of atherosclerosis, but histological investigations are limited. The aim of this study is to determine whether calcifications in the iICA are present in atherosclerotic plaques, or in other parts of the arterial wall. METHODS—: Thirty-nine iICAs were histologically assessed, using digital microscopy to quantify the amount of calcification in the different layers of the arterial wall. RESULTS—: Calcifications were found in the intima, around the internal elastic lamina and in the medial layer of the arterial wall. In 71% of the arteries, internal elastic lamina calcification contributed most to the total calcified cross-sectional surface area. Internal elastic lamina calcification was unrelated to the occurrence of atherosclerotic intimal lesions. Intimal calcifications were most often associated with atherosclerotic lesions, but also many noncalcified atherosclerotic lesions were found. CONCLUSIONS—: In the iICA, calcifications are predominantly present around the internal elastic lamina, suggesting that this nonatherosclerotic type of calcification contributes to the previously observed increased risk of stroke in patients with iICA calcifications

Predominance of nonatherosclerotic internal elastic lamina calcification in the intracranial internal carotid artery

Background and Purpose - Calcification of the intracranial internal carotid artery (iICA) is an independent risk factor for stroke. These calcifications are generally seen as manifestation of atherosclerosis, but histological investigations are limited. The aim of this study is to determine whether calcifications in the iICA are present in atherosclerotic plaques, or in other parts of the arterial wall. Methods - Thirty-nine iICAs were histologically assessed, using digital microscopy to quantify the amount of calcification in the different layers of the arterial wall. Results - Calcifications were found in the intima, around the internal elastic lamina and in the medial layer of the arterial wall. In 71% of the arteries, internal elastic lamina calcification contributed most to the total calcified cross-sectional surface area. Internal elastic lamina calcification was unrelated to the occurrence of atherosclerotic intimal lesions. Intimal calcifications were most often associated with atherosclerotic lesions, but also many noncalcified atherosclerotic lesions were found. Conclusions - In the iICA, calcifications are predominantly present around the internal elastic lamina, suggesting that this nonatherosclerotic type of calcification contributes to the previously observed increased risk of stroke in patients with iICA calcifications

Computed Tomographic Distinction of Intimal and Medial Calcification in the Intracranial Internal Carotid Artery

BACKGROUND: Intracranial internal carotid artery (iICA) calcification is associated with stroke and is often seen as a proxy of atherosclerosis of the intima. However, it was recently shown that these calcifications are predominantly located in the tunica media and internal elastic lamina (medial calcification). Intimal and medial calcifications are thought to have a different pathogenesis and clinical consequences and can only be distinguished through ex vivo histological analysis. Therefore, our aim was to develop CT scoring method to distinguish intimal and medial iICA calcification in vivo. METHODS: First, in both iICAs of 16 cerebral autopsy patients the intimal and/or medial calcification area was histologically assessed (142 slides). Brain CT images of these patients were matched to the corresponding histological slides to develop a CT score that determines intimal or medial calcification dominance. Second, performance of the CT score was assessed in these 16 patients. Third, reproducibility was tested in a separate cohort. RESULTS: First, CT features of the score were circularity (absent, dot(s), <90°, 90-270° or 270-360°), thickness (absent, ≥1.5mm, or <1.5mm), and morphology (indistinguishable, irregular/patchy or continuous). A high sum of features represented medial and a lower sum intimal calcifications. Second, in the 16 patients the concordance between the CT score and the dominant calcification type was reasonable. Third, the score showed good reproducibility (kappa: 0.72 proportion of agreement: 0.82) between the categories intimal, medial or absent/indistinguishable. CONCLUSIONS: The developed CT score shows good reproducibility and can differentiate reasonably well between intimal and medial calcification dominance in the iICA, allowing for further (epidemiological) studies on iICA calcification

Computed Tomographic Distinction of Intimal and Medial Calcification in the Intracranial Internal Carotid Artery

BACKGROUND: Intracranial internal carotid artery (iICA) calcification is associated with stroke and is often seen as a proxy of atherosclerosis of the intima. However, it was recently shown that these calcifications are predominantly located in the tunica media and internal elastic lamina (medial calcification). Intimal and medial calcifications are thought to have a different pathogenesis and clinical consequences and can only be distinguished through ex vivo histological analysis. Therefore, our aim was to develop CT scoring method to distinguish intimal and medial iICA calcification in vivo. METHODS: First, in both iICAs of 16 cerebral autopsy patients the intimal and/or medial calcification area was histologically assessed (142 slides). Brain CT images of these patients were matched to the corresponding histological slides to develop a CT score that determines intimal or medial calcification dominance. Second, performance of the CT score was assessed in these 16 patients. Third, reproducibility was tested in a separate cohort. RESULTS: First, CT features of the score were circularity (absent, dot(s), <90°, 90-270° or 270-360°), thickness (absent, ≥1.5mm, or <1.5mm), and morphology (indistinguishable, irregular/patchy or continuous). A high sum of features represented medial and a lower sum intimal calcifications. Second, in the 16 patients the concordance between the CT score and the dominant calcification type was reasonable. Third, the score showed good reproducibility (kappa: 0.72 proportion of agreement: 0.82) between the categories intimal, medial or absent/indistinguishable. CONCLUSIONS: The developed CT score shows good reproducibility and can differentiate reasonably well between intimal and medial calcification dominance in the iICA, allowing for further (epidemiological) studies on iICA calcification

Nationwide practice in CT-based preoperative staging of colon cancer and concordance with definitive pathology

Introduction: In an era of exploring patient-tailored treatment options for colon cancer, preoperative staging is increasingly important. This study aimed to evaluate completeness and reliability of CT-based preoperative locoregional colon cancer staging in Dutch hospitals. Materials and methods: Patients who underwent elective oncological resection of colon cancer without neoadjuvant treatment in 77 Dutch hospitals were evaluated between 2011 and 2021. Completeness of T-stage was calculated for individual hospitals and stratified based on a 60% cut-off. Concordance between routine CT-based preoperative locoregional staging (cTN) and definitive pathological staging (pTN) was examined. Results: A total of 59,558 patients were included with an average completeness of 43.4% and 53.4% for T and N-stage, respectively. Completeness of T-stage improved from 4.9% in 2011–2014 to 74.4% in 2019–2021. Median completeness for individual hospitals was 53.9% (IQR 27.3–80.5%) and were not significantly different between low and high-volume hospitals. Sensitivity and specificity for T3-4 tumours were relatively low: 75.1% and 76.0%, respectively. cT1-2 tumours were frequently understaged based on a low negative predictive value of 56.8%. Distinction of cT4 and cN2 disease had a high specificity (&gt;95%), but a very low sensitivity (&lt;50%). Positive predictive values of &lt;60% indicated that cT4 and cN1-2 were often overstaged. Completeness and time period did not influence reliability of staging. Conclusion: Completeness of locoregional staging of colon cancer improved during recent years and varied between hospitals independently from case volume. Discriminating cT1-2 from cT3-4 tumours resulted in substantial understaging and overstaging, additionally cT4 and cN1-2 were overstaged in &gt;40% of cases.</p