Small Calcifications Research Articles

Targeting TREM2 signaling shows limited impact on cerebrovascular calcification.

Brain calcification, the ectopic mineral deposits of calcium phosphate, is a frequent radiological finding and a diagnostic criterion for primary familial brain calcification. We previously showed that microglia curtail the growth of small vessel calcification via the triggering receptor expressed in myeloid 2 (TREM2) in the Pdgfb ret/ret mouse model of primary familial brain calcification. Because boosting TREM2 function using activating antibodies has been shown to be beneficial in other disease conditions by aiding in microglial clearance of diverse pathologies, we investigated whether administration of a TREM2-activating antibody could mitigate vascular calcification in Pdgfb ret/ret mice. Single-nucleus RNA-sequencing analysis showed that calcification-associated microglia share transcriptional similarities to disease-associated microglia and exhibited activated TREM2 and TGFβ signaling. Administration of a TREM2-activating antibody increased TREM2-dependent microglial deposition of cathepsin K, a collagen-degrading protease, onto calcifications. However, this did not ameliorate the calcification load or alter the mineral composition and the microglial phenotype around calcification. We therefore conclude that targeting microglia with TREM2 agonistic antibodies is insufficient to demineralize and clear vascular calcifications.

Automated differentiation of calcifications and their clusters on the mammography image: the outcomes of the computer aided diagnosis system module

INTRODUCTION: Previously we developed the computer aided detection system (CAD) for mammography MammCheck II that increased the detection rate of small and difficult to detect breast carcinomas (BC). However this system was not specifically designed for calcification detection and discrimination. On the other hand, the calcifications had no influence on the CAD capability to detect BCs that appeared as a focal lesions.OBJECTIVE: To develop the approach for automated differentiation of benign and suspicious calcifications on the mammography images and assess its clinical value.MATERIALS AND METHODS: For the developed software testing we used a set of 390 mammography images with calcifications of all possible types (278 images with benign and 112 images with suspicious calcifications). For classification we used linear support vector machine (SVM) model, that was trained on the set of 126 images (70 — benign and 56 — suspicious). We developed two SVM models: with no vascular calcification analysis and with it. Statistics: for comparison between the normally distributed samples we used the Student’s T-test, for non-normally distributed — Wilcoxon signed-rank or Chi-square tests. For correlation testing of normally distributed samples the Paerson coefficient was calculated, for non-normally distributed samples — the Spearman or Kendall correlation coefficients. The statistical significance corresponded to Р-values <0,05.RESULTS: During the testing of the first model version with no vascular calcification analysis we discovered the similarity of small early vascular calcifications and the suspicious ones. As a result this model falsely classified 14 of 23 (60.87%) vascular calcification clusters as suspicious. Therefore the model was improved. The final discrimination results for all calcification types (both benign and suspicious) obtained with the help of improved model were the following: true positive conclusions — 375/390 (96.15%), false positive conclusions — 15/390 (3.84%). In both cases when suspicious calcifications were classified as benign the wrong results were een only on one mammography view. At the same time, on another view the suspicious calcifications were correctly classified.DISCUSSION: During the CAD development it seems important not only mark the suspicious areas but also suppress false positive markings corresponding to the obviously benign lesions. However it is important during this operation not to suppress the true positive markings. Therefore such systems are inevitably characterized by a certain shift to decreased prognostic value of suspicious markings at the expense of the highest possible prognostic value of benign markings. In our viewpoint, the developed approach meets this requirement. Moreover, its integration into the CAD allows to suppress the markings of soft tissue lesions associated with typical benign calcifications, appeared on the previous processing steps. This capability may decrease the false positive rate of the main CAD module.CONCLUSION: The developed approach to benign and suspicious calcification discrimination (version with vascular calcification analysis) on the mammography image provided the sensitivity — 98.21%, specificity — 95.32%, negative predictive value (benign marking) — 99.25%, positive predictive value (suspicious marking) — 89.43%.

7328 A case of Adrenal Calcifications in a Patient with Familial Cerebral Cavernous Malformations

Abstract Disclosure: R.I. Dorin: None. L.E. Aguirre: None. M. Bomgardner: None. Background: Familial syndromes of cerebral cavernous malformation (fCCM) having autosomal dominant inheritance and variable penetrance and expression have been linked to loss of function mutations at three genetic loci. The association of small focal adrenal calcifications with fCCM was only recently recognized in a New Mexican cohort of subjects predominately carrying the founder common Hispanic mutation in the CCM1 locus (stop codon Q455X in the Krev1 interaction trapped gene 1 [KRIT1]). We report a case of bilateral, focal adrenal calcifications in a patient affected by fCCM. Clinical Case: A 72-year-old Hispanic male with past medical history of intracranial CCM was referred for osteoporosis and hyperthyroidism due to multinodular goiter. Small focal calcifications of the adrenal glands were incidentally noted on prior imaging studies. There was no history of anticoagulant use, adrenal hemorrhage, or systemic/adrenal infection. The patient was without clinical manifestations of adrenal insufficiency, morning cortisol and plasma ACTH concentrations were normal, and exam was negative for hyperpigmentation or cutaneous vascular malformations. Brain MRI revealed the presence of over 100 parenchymal CCM lesions. A family history of CCM was reported in multiple family members, including 7/10 siblings. Conclusion: In addition to cutaneous malformations, small focal adrenal calcifications are now recognized as one of the extra-neurological manifestations of fCCM, particularly in patients harboring the common Hispanic CCM1/KRIT1 mutation. Whether adrenal calcifications are observed in fCCM patients having other mutations of KRIT1 or other genetic loci of fCCM (CCM2 or PDCD10) remains to be determined. The focal adrenal calcifications are believed to be result of dyssynchronous, subclinical hemorrhagic events related to vascular malformations in the adrenal gland. These findings implicate a role for KRIT1 in endothelial development in the adrenal gland in addition to established role in CNS, spinal cord, and skin. Our patient appeared had normal adrenocortical function, as expected for the focal nature of the adrenal lesions. Though adrenal function has not been evaluated in fCCM patients, there are no reports of primary adrenal insufficiency in fCCM in the literature. Adrenal calcifications may be considered to represent an imaging biomarker for fCCM, and fCCM should be included in the differential diagnosis of adrenal calcifications. The incidental recognition of characteristic small, focal adrenal calcifications in either bilateral or unilateral adrenal glands should prompt evaluation for fCCM.

Calcific uraemic arteriolopathy: A rare but devastating complication of end-stage renal failure

Calcific uraemic arteriolopathy is a rare complication of end-stage renal failure. It has a grave prognosis with 1-year survival of under 50%. It occurs due to subcutaneous small vessel calcification, thrombosis, with subsequent tissue necrosis. Calcific uraemic arteriolopathy is a rare complication of end-stage renal failure. It carries a grave prognosis with 1-year survival of under 50%. It occurs due to subcutaneous small vessel calcification, thrombosis, with subsequent tissue necrosis. We described a case of calcific uraemic arteriolopathy in a 58-year-old man who presented with violaceous indurations over bilateral lower limbs, as well as large necrotic ulcer with adjacent eschars at the lower abdomen. Although skin biopsy is the gold standard for diagnosis, it is often avoided due to potential poor wound healing. On the other hand, in radiographs or computed tomography, fine linear or serpiginous subcutaneous calcifications are typical manifestations, which represent underlying small vessel calcifications. Radiological examinations, therefore, play an important role to establish the diagnosis.

Large (≥3-Millimeter) Parenchymal Brain Calcified Cysticerci Are More Often Associated with Hippocampal Atrophy than Smaller Ones in Seizure-Free Individuals with a Single Lesion.

Calcified cysticerci are often associated with hippocampal atrophy (HA). While most studies suggest that repetitive seizures cause HA in these patients, others have demonstrated that HA may also occur in persons without epilepsy. Little is known about mechanisms triggering HA in seizure-free individuals with calcified cysticerci. Here, we aimed to assess whether the size of the calcification is associated with HA. Using a population-based design, we selected apparently seizure-free individuals with a single calcified cysticercus in whom interictal paroxysmal activity and other causes of HA have been discarded. A total of 55 individuals (mean age, 58.3 ± 13 years, 62% women) fulfilled inclusion criteria. Unadjusted and multivariate models were fitted to assess the association between the size of the calcification dichotomized into <3 mm and ≥3 mm (exposure) and the presence of HA (outcome). Sixteen participants (29%) had HA, which was asymmetric in eight (50%) cases. Hippocampal atrophy was noted in 11/20 (55%) participants with large calcifications and in 5/35 (14%) with small calcifications (P = 0.001). A multivariate logistic regression model showed a significant association between the presence of large calcifications and HA, after adjustment for relevant confounders (odds ratio: 7.78; 95% CI: 1.72-35.1). Participants with calcifications ≥3 mm in diameter were 7.8 times more likely to have HA than those with smaller ones. Study results open avenues of research for the use of agents to prevent HA progression.

Imaging methods in monitoring gout - a pictorial essay.

We present a pictorial essay based on the case of a 52-year-old man suffering from chronic gout, who was followed up for seven years. During this period of time, radiographs, ultrasonography, and dualenergy computed tomography were performed several times, revealing severe progression of gout. This was most likely due to the lack of patient compliance. Inflammatory and destructive lesions were observed in the wrists, in the metacarpophalangeal and proximal interphalangeal joints. Ultrasonography showed tenosynovitis, synovitis with small calcifications in the synovial membrane. Radiographs obtained in later stages showed tophi and bone erosions. Dual-energy computed tomography showed deposits of monosodium urate crystals in different locations, which increased in volume over time. This modality can be used to confirm a clinical diagnosis of gout, especially in early stages of the disease, and to follow up the treatment.

Searching for a twinkling artefact in breast microcalcifications using B-flow ultrasonic non-doppler technology: a prospective study

INTRODUCTION: The rapid rejuvenation of breast cancer in recent years has made it necessary to look for non-X-ray methods of imaging microcalcifications in women not yet covered by mammography screening. Developing technologies to see these microcalcifications on ultrasound is a promising goal, potentially reducing the number of unnecessary biopsies.OBJECTIVE: Evaluation of factors influencing the ability of the B-flow technique to detect the presence of a flickering artifact in patients with microcalcifications detected by mammography.MATERIALS AND METHODS: A prospective study of 57 patients with microcalcifications detected on mammograms was conducted. The Nondoppler technology of B-flow ultrasound examination was used for targeted ultrasound with the search for these areas during ultrasound. The possibilities of visualization of the twinkle artifact were evaluated for various microcalcifications in size, distribution, their number, and for pathological processes of different nature. Images in B-flow mode were found to be positive when a bright local flash occurred against a dark background in B-mode. Verification of diagnostic findings was performed by ultrasound-guided core- biopsy from areas with a twinkle artifact (in the presence of an imaging area during ultrasound) or with stereotactic biopsy (in the absence of visualization of the suspicious area with ultrasound with B-flow).Statistics: The ANOVA test was used for triple pairwise comparisons between positive groups. The p&lt;0.05 value was considered statistically significant.RESULTS: According to the results of the study, out of 57 cases with microcalcifications, 34 (60%) recorded a twinkle artifact. The amount of microcalcifications with a visualized twinkle effect in B-flow was significantly higher in benign processes 34 (82.9%) out of 41, and less often in malignant 8 (50%) out of 16 (p=0.035). The effect of calcification morphology on the mammogram on their detection by ultrasound in the B-flow mode (p=0.035) was statistically significant. The most frequently manifested twinkle artifact were rounded, regular-shaped calcifications in 19 (95%) out of 20, which were found in granulomatous mastitis, fibrocystic changes, fibroadenomas, sclerosing adenosis, as well as polymorphic calcifications in 7 (63.6%) of 11. In the B-flow mode, it was not possible to obtain a twinkle artifact mainly with point small calcifications of 9 (69.2%) out of 13, and in all cases with linear or linear branching calcifications. In amorphous microcalcifications, the characteristics of background echogenicity and the presence or absence of a nodal component in the gray scale mode had a much greater influence on the appearance of the twinkle effect in the normal B-mode, whereas in the B-flow mode, these characteristics did not have a decisive effect on the appearance of a flickering artifact (p=0.8). The density of distribution of microcalcifications, the size of calcifications, the final pathomorphology, mammography characteristics, the background environment during ultrasound by the presence or absence of nodular formation and anechoic zones, did not affect the appearance of a bright flash in the B-flow mode.DISCUSSION: The density of calcification distribution was not decisive for the appearance of a shimmering artifact in the B-flow mode. The flicker artifact is recorded both in grouped microcalcifications and in single ones. B-flow can help to detect calcifications that are not visible in the usual B-flow mode due to the lack of pronounced tissue contrast. But this artifact cannot be used to differentiate between benign and malignant processes.CONCLUSION: The B-flow technique is promising for clarifying the twinkle artifact in the detected microcalcifications on the mammogram, which could potentially increase the incidence of ultrasound-guided trephine biopsies by detecting more areas with microcalcification accumulations.

AUTOMATIC IDENTIFICATION OF ISOLATED CALCIFICATIONS AND THEIR ACCUMULATIONS ON MAMMOGRAMS

Although microcalcinates usually are hyperattenuated, which makes them hyperintensive on mammograms, breast cancer is characterized by their small size, which, combined with the small size of their clusters, makes it difficult to identify them, especially against a dense background, which is often noted in fibrous changes in the breast parenchyma. The purpose of the study is to create and evaluate the effectiveness of the block for automatic identification of calcifications and their accumulations on mammograms. Material and methods. Mammograms of patients with suspicious (136 mammograms of 67 patients), as well as benign (299 mammograms of 151 patients) calcifications of various types were analyzed using a proprietary software package. Research results. After analyzing benign calcifications, the system marked all cases (100%) of calcified sediment, rod-shaped, vascular calcifications; 33 out of 36 (92.7%) cases of dystrophic, 66 out of 70 cases (94.3%) of rounded and 12 out of 15 (80%) cases of point calcifications in all patients; as well as 2 out of 3 cases of cutaneous calcifications in 1 out of 2 patients, 103 out of 106 (97.2%) cases of flaky calcifications in 51 out of 52 (98.1%) patients and 19 out of 22 cases (86.4%) of eggshell type calcifications in 10 out of 11 patients (90.9%). Among suspicious calcifications, the system marked 33 out of 39 cases (84.6%) of large heterogeneous calcifications, all 6 cases of small linear branching calcifications and 37 out of 39 (94.9%) cases of small polymorphic calcifications in all patients, as well as 30 out of 36 (83.3%) cases of amorphous calcifications in 15 out of 16 (93.7%) patients and 12 out of 16 (75.0%) cases of small linear calcifications in 6 out of 8 (75.0%) patients. All cases of unmarked suspicious calcifications corresponded to high-intensity soft-tissue shadows associated with indistinctly defined calcifications, which were labeled by the MammCheck II system previously developed by the authors. The frequency of false positive labels was 0.31 per mammogram. Conclusions. Benign calcifications were marked on 282 out of 299 images (94.3%) in 148 out of 151 (98.0%) patients, suspicious calcifications – on 118 out of 136 images (86.8%) in 64 out of 67 patients (95.5%).

Testicular biopsies in men with testicular microlithiasis and additional risk factors for cancer: A case series.

Testicular microlithiasis is the presence of small calcifications in the testicular parenchyma. The association between testicular microlithiasis and germ cell neoplasia in situ, a precursor to testicular cancer, is still unclear. To determine the incidence of germ cell neoplasia in situ in men with testicular microlithiasis and evaluate the indication for testicular biopsy according to risk factors in the form of male infertility/reduced semen quality, testicular atrophy, and history of cryptorchidism. This retrospective case series included all patients diagnosed with testicular microlithiasis who underwent testicular biopsies at three hospitals in Denmark between 2007 and 2021. The medical records of 167 patients were reviewed, and data on patient demographics, testicular microlithiasis characteristics, risk factors, histological findings, and treatments were collected. The main outcome measure was the incidence of germ cell neoplasia in situ in relation to each risk factor. The data were analyzed using descriptive statistics. Logistic regression was used to examine the odds ratio of germ cell neoplasia in situ in patients with testicular microlithiasis and testicular atrophy. Germ cell neoplasia in situ was found in 13 out of 167 patients (7.8% [95% confidence interval: 4.3, 13.2]). Eleven of these had testicular atrophy resulting in a significantly higher incidence in this group than other risk factors (odds ratio 9.36 [95% confidence interval: 2.41, 61.88]; p=0.004). The study comprises the largest cohort to date of men who have undergone testicular biopsies because of testicular microlithiasis and additional risk factors. Limitations include its retrospective design, and relatively low absolute numbers of patients with germ cell neoplasia in situ on biopsies. This study found that men with testicular microlithiasis and testicular atrophy are at an increased risk of germ cell neoplasia in situ. Additionally, our results indicate that biopsies should be considered in men with a combination of subfertility and bilateral testicular microlithiasis. Our findings do not support testicular biopsies for men with testicular microlithiasis and other risk factors.

Small dense low-density lipoprotein cholesterol and coronary artery calcification in the Multi-Ethnic Study of Atherosclerosis.

Elevated small dense LDL cholesterol (sd-LDL-C) increases atherosclerotic cardiovascular disease (CVD) risk. Although coronary artery calcification (CAC) is widely used for predicting CVD events, few studies have examined the relationship between sd-LDL-C and CAC. This study included 4672 individuals with directly measured baseline sd-LDL-C and CAC from the Multi-Ethnic Study of Atherosclerosis [mean (standard deviation) age: 61.9 (10.4) years; 52.5% women; 47.3% with baseline CAC (mean score >0)]. We used multi-variable general linear models and restricted cubic splines with the goodness of fit testing to evaluate the association of sd-LDL-C with the presence of CAC. Odds ratios [OR (95% confidence interval)] were adjusted for demographics and cardiovascular risk factors, including estimated total LDL-C. Higher quartiles of sd-LDL-C were associated with the presence of CAC, even after accounting for total LDL-C. Compared with the lowest quartile of sd-LDL-C, participants in Quartiles 2, 3, and 4 had higher odds for the presence of baseline CAC [Quartile 2 OR: 1.24 (1.00, 1.53); Quartile 3 OR: 1.51 (1.19, 1.93); and Quartile 4 OR 1.59 (1.17, 2.16)]. Splines suggested a quadratic curvilinear relationship of continuous sd-LDL-C with CAC after adjustment for demographics and CVD risk factors (quadratic vs. first-order sd-LDL-C terms likelihood ratio test: P = 0.015), but not after accounting for total LDL-C (quadratic vs. first-order terms: P = 0.156). In a large, multi-ethnic sample without known CVD, higher sd-LDL-C was associated with the presence of CAC, above and beyond total LDL-C. Whether selective direct measurement of sd-LDL-C is indicated to refine cardiovascular risk assessment in primary prevention warrants further investigation.

Analysis of fibrocalcific aortic valve stenosis: computational pre-and-post TAVR haemodynamics behaviours.

Fibro-calcific aortic valve (AV) diseases are characterized by calcium growth or accumulation of fibrosis in the AV tissues. Fibrocalcific aortic stenosis (FAS) rises specifically in females, like calcification-induced aortic stenosis (CAS), may eventually necessitate valve replacement. Fluid-structure-interaction (FSI) computational models for severe CAS and FAS patients were developed using lattice Boltzmann method and multi-scale finite elements (FE). Three parametric AV models were introduced: pathology-free of non-calcified tri-and-bicuspid AVs with healthy collagen fibre network (CFN), a FAS model incorporated a thickened CFN with embedded small calcification volumes, and a CAS model employs healthy CFN with embedded high calcification volumes. The results indicate that the interaction between calcium deposits, adjacent tissue and fibres crucially influences haemodynamics and structural reactions. A fourth model of transcatheter aortic valve replacement (TAVR) post-procedure outcomes was created to study both CAS and FAS. TAVR-CAS had a higher maximum contact pressure and lower anchoring area than TAVR-FAS, making it prone to aortic tissue damage and migration. Finally, although the TAVR-CAS offered a larger opening area, its paravalvular leakage was higher. This may be attributed to a similar thrombogenicity potential characterizing both models. The computational framework emphasizes the significance of mechanobiology in FAS and underscores the requirement for tissue modelling at multiple scales.

Pathomorphological characteristics of tuberculous placenta and its clinical implication

BackgroundThe study of pathologic diagnosis of placental TB is rare. The aim of this study is analyzing the pathomorphological characteristics of tuberculosis (TB) placenta during pregnancy and its clinical significance.MethodsNineteen cases of placental tissue specimens during pregnancy were collected from June 2015 to February 2022 at Shanghai Public Health Clinical Center, the only inpatient center for pregnant women with TB in Shanghai, China. Hematoxylin-eosin staining, acid-fast staining, and molecular testing were applied to analyze them comprehensively in combination with clinical information.ResultsAmong the 19 cases, 7 cases caused intrauterine stillbirth, 3 cases received artificial abortion required by the pregnant woman, the other 9 cases received standard delivery and the infants survived, however, 3 of them were low-weight preterm infants, and another 1 case suffered mild intrauterine asphyxia. The 9 surviving infants were followed-up, of which 3 cases got congenital TB. For pathological characteristics of placental tissues under light microscopy, there were 3 cases of epithelioid granuloma formation, 13 cases of acute fetal membranitis, 4 cases of caseous necrosis, 7 cases of inflammatory necrosis, 10 cases of coagulative necrosis, and 6 cases with small focal calcifications. All placental tissues were positive for acid-fast staining and polymerase chain reaction (PCR). Molecular pathological diagnosis showed that 18 cases were positive for Mycobacterium tuberculosis, with 1 case not having received examination.ConclusionsCombining acid-fast staining and molecular pathological testing is helpful for accurately diagnosing placental TB.

Morphometric and immuno-biochemical markers of placenta in patients with uterine eclampsia

Purpose: to study the segmentation of organometric and immuno-biochemical digital indicators in ewes with ESO at the end of gestation.Materials and methods. The experiment involved three flocks of Tsygai, Volgograd and Stavropol breeds, each with 700 suyag sheep. Placental tissue samples were taken from clinically healthy and sick pregnant ewes, which were placed in 10% neutral formalin. Using a Cytadel 2000 histoprocessor (Shendon), the obtained samples were clarified in chloroform and enclosed in a Histomix paraffin medium (Biovitrum). Histosections were prepared on a rotary microtome (MICROM HM340E). Using the AxioScope.A1 (ZEISS) microscope, histopreparations were photographed and processed using the ZENpro 2012 (ZEISS) program. According to Schmidt and Thannhauser, the RNA content was determined using a two-wave spectrophotometer in UV. The activity of the G-6-Phase was studied by Swanson. In vacuum tubes Vacuette ™ (Austria), blood samples were taken in the morning before feeding, from the jugular vein. Results. In sheep with eclampsia, a decrease in the total mass of the placenta, its cotiledons, as well as an increase in the length of the umbilical cord, in which stroma sclerosis is noted in the vascular wall, was observed. Small calcification foci were found in the tissues of the afterbirth, and small terminal villi are located around the stem villi near the vascular membrane, tightly adjacent to them. The proportion of syncytiotrophoblast of crypts of carbuncles and villi of the chorion of cotyledons of mature syncytium decreases in comparison with physiologically occurring severity. The content of RNA in its subcellular fractions is mainly concentrated in the microsomal fraction, 18% - in mitochondria and 7% - in the nuclear fraction. Albumins in pregnant ewes with eclampsia were reduced by 1.35 times. BASC and phagocytic activity of leukocytes in queens with eclampsia of pregnant sheep is reduced 15 days before lambing, which poses a threat to the reproductive health of the mother and the viability of newborn lambs.

An in vitro model system based on calcium- and phosphate ion-induced hMSC spheroid mineralization

A challenge in regenerative medicine is creating the three-dimensional organic and inorganic in vitro microenvironment of bone, which would allow the study of musculoskeletal disorders and the generation of building blocks for bone regeneration. This study presents a microwell-based platform for creating spheroids of human mesenchymal stromal cells, which are then mineralized using ionic calcium and phosphate supplementation. The resulting mineralized spheroids promote an osteogenic gene expression profile through the influence of the spheroids’ biophysical environment and inorganic signaling and require less calcium or phosphate to achieve mineralization compared to a monolayer culture. We found that mineralized spheroids represent an in vitro model for studying small molecule perturbations and extracellular mediated calcification. Furthermore, we demonstrate that understanding pathway signaling elicited by the spheroid environment allows mimicking these pathways in traditional monolayer culture, enabling similar rapid mineralization events. In sum, this study demonstrates the rapid generation and employment of a mineralized cell model system for regenerative medicine applications.

Treatment of calcific arterial disease via enhancement of autophagy using GSK343

Vascular calcification is a hallmark of atherosclerotic disease and serves as a strong predictor and risk factor for cardiovascular events. Growing evidence suggests that autophagy may play a protective role in early atherosclerosis. The precise effects of autophagy on VSMC-mediated calcification remain unknown. In this study, we utilized multi-omic profiling to investigate impaired autophagy at the transcriptional level as a key driver of VSMC calcification. Our findings revealed that impaired autophagy is an essential determinant of VSMC calcification. We observed that an osteogenic environment affects the open chromatin status of VSMCs, compromising the transcriptional activation of autophagy initiation genes. Invivo experiments involve pharmacological and genetic activation of autophagy using mouse models of spontaneous large (Mgp-/-) and small (Abcc6-/-) artery calcification. Taken together, these data advance our mechanistic understanding of vascular calcification and provide important insights for a broad range of cardiovascular diseases involving VSMC phenotype switch.

FRI195 Tuberculosis and Adrenal Glands: The Great Forgotten

Abstract Disclosure: I. Vina: None. R. Sánchez: None. I.C. Fernández: None. C. Vázquez: None. Background: Tuberculous adrenalitis is an extremely rare cause of Addison disease in developed countries. Since more than 80% of the primary adrenal insufficiency cases in the developed world are caused by autoimmune disease, tuberculous adrenalitis often go unnoticed. The aim of this case report is to remember that, even if it is not frequent, TB cannot be overlooked as a cause of longstanding primary adrenal insufficiency, even without evidence of pulmonary or extra glandular TB disease. Herein, we reported a case of bilateral tuberculous adrenalitis, wherein the patient initially presented with gastrointestinal symptoms, hyperpigmentation, bilateral adrenal masses, and no evidence of extra-adrenal tuberculosis. Case report: A 57-year-old woman from Madrid with no medical relevant history, was admitted to our hospital with 4 months of evolution of asthenia, weight loss (-8kg) and nausea that in recent days has been accompanied by fever and anorexia. He also refers progressive hyperpigmentation for the past 3 years. Denies recent travel abroad. On physical examination hypotension (80/53 mmHg) and generalized hyperpigmentation predominantly in the oral mucosa stand out. Blood test: Glu: 41 mg/dL, Na+: 122 mmol/L, K+: 4.8 mmol/L, ACTH: 922 pg/mL, Cortisol: 4.63 ug/dL, Anti-Hydroxylase Ab and Anti-Adrenal glands Ab: negative A computed tomography scan of the abdomen with intravenous contrast revealed bilaterally enlarged adrenal glands with small bilateral calcifications (12-18mm). TB QuantiFERON test: positive. She was initially treated with saline serum and intravenous hydrocortisone causing her symptoms to improve significantly in a few days and was subsequently discharged on hydrocortisone and fludrocortisone and proper treatment for TB Adrenalitis and follow-up in outpatient clinics. Conclusions: Although not frequent, infectious causes should always be kept in mind, such as the etiology of adrenal insufficiency in a patient with long-term compatible symptoms, even though it is a developed country, given world globalization, which makes infectious diseases highly transmissible between countries and continents. Presentation: Friday, June 16, 2023

Technical note: Exploring the detectability of coronary calcification using ultra-high-resolution photon-counting-detector CT.

Coronary calcification is a strong indicator of coronary artery disease, and patients with a "zero" coronary calcification score have a much lower risk of future cardiac events than those with even small amounts of calcium. However, false-negative (incorrect zero scores) may occur if small calcifications are missed at CT due to limited spatial resolution. To demonstrate lower limits of detection for coronary calcification using an ultra-high-resolution (UHR) mode on a clinical photon-counting-detector CT (PCD-CT), compared to a conventional energy-integrating-detector CT (EID-CT). Chicken eggshell fragments (0.4-0.8mm) mimicking coronary calcifications were scanned on a clinical PCD-CT (NAEOTOM Alpha) in UHR mode and a conventional EID-CT (SOMATOM Force) with matched tube potential and radiation dose levels to the PCD-CT. PCD-CT images were reconstructed with a sharp kernel (Qr68) and a quantum iterative algorithm (QIR-3). Two sets of EID-CT images were reconstructed: routine clinical kernel (Qr36, ADMIRE-3) and a sharper kernel (Qr54) with similar noise to PCD-CT images. With institutional review board approval, in vivo exams performed with the PCD-CT in UHR mode were compared against patients' clinical EID-CT exams. The visibility of calcifications on PCD-CT and EID-CT images was assessed and compared qualitatively. PCD-CT images visualized all calcified fragments, while EID-CT failed to detect those below 0.6mm using a routine protocol. EID-CT with Qr54 improved visibility but distorted boundaries. Calcifications were less visible on EID-CT than PCD-CT as phantom sizes increased. 0.6- and 0.7-mm calcified fragments were barely visible on 35- and 40-cm phantom EID-CT images. Patient cases showed small calcifications missed on EID-CT but detected on PCD-CT. At matched radiation dose, PCD-CT in UHR mode provided higher spatial resolution and improved the detectability of small calcified fragments for different phantom/patient sizes in comparison to EID-CT.

Impact of super-resolution and image acquisition on the detection of calcifications in digital breast tomosynthesis.

A virtual clinical trial (VCT) method is proposed to determine the limit of calcification detection in tomosynthesis. Breast anatomy, focal findings, image acquisition, and interpretation (n = 14 readers) were simulated using screening data (n = 660 patients). Calcifications (0.2-0.4 mm3) were inserted into virtual breast phantoms. Digital breast tomosynthesis (DBT) acquisitions were simulated assuming various acquisition geometries: source motion (continuous and step-and-shoot), detector element size (140 and 70µm), and reconstructed voxel size (35-140µm). VCT results were estimated using multiple-reader multiple-case analyses and d' statistics. Signal-to-noise (SNR) analyses were also performed using BR3D phantoms. Source motion and reconstructed voxel size demonstrated significant changes in the performance of imaging systems. Acquisition geometries that use 70µm reconstruction voxel size and step-and-shoot motion significantly improved calcification detection. Comparing 70 with 100µm reconstructed voxel size for step-and-shoot, the ΔAUC was 0.0558 (0.0647) and d' ratio was 1.27 (1.29) for 140µm (70µm) detector element size. Comparing step-and-shoot with a continuous motion for a 70µm reconstructed voxel size, the ΔAUC was 0.0863 (0.0434) and the d' ratio was 1.40 (1.19) for 140µm (70µm) detector element. Small detector element sizes (e.g., 70µm) did not significantly improve detection. The SNR results with the BR3D phantom show that calcification detection is dependent upon reconstructed voxel size anddetector element size, supporting VCT results with comparable agreement (ratios: d' = 1.16 ± 0.11, SNR = 1.34 ± 0.13). DBT acquisition geometries that use super-resolution (smaller reconstructed voxels than the detector element size) combined with step-and-shoot motion have the potential to improve the detection of calcifications. Calcifications may not always be discernable in tomosynthesis because of differences in acquisition and reconstruction methods. VCTs can identify strategies to optimize acquisition and reconstruction parameters for calcification detection in tomosynthesis, most notably through super-resolution in the reconstruction. • Super-resolution improves calcification detection and SNR in tomosynthesis; specifically, with the use of smaller reconstruction voxels. • Calcification detection using step-and-shoot motion is superior to that using continuous tube motion. • A detector element size of 70µm does not provide better detection than 140µm for small calcifications at the threshold of detectability.

Calcified plaque harboring lipidic materials associates with no-reflow phenomenon after PCI in stable CAD

Calcified atheroma has been viewed conventionally as stable lesion which less likely increases no-reflow phenomenon. Given that lipidic materials triggers the formation of calcification, lipidic materials could exist within calcified lesion, which may cause no-reflow phenomenon after PCI. The REASSURE-NIRS registry (NCT04864171) employed near-infrared spectroscopy and intravascular ultrasound imaging to evaluate maximum 4-mm lipid-core burden index (maxLCBI4mm) at target lesions containing small (maximum calcification arc < 180°: n = 272) and large calcification (maximum calcification arc ≥ 180°: n = 189) in stable CAD patients. The associations of maxLCBI4mm with corrected TIMI frame count (CTFC) and no-reflow phenomenon after PCI were analyzed in patients with target lesions containing small and large calcification, respectively. No-reflow phenomenon occurred in 8.0% of study population. Receiver-operating characteristics curve analyses revealed that optimal cut-off values of maxLCBI4mm for predicting no-reflow phenomenon were 585 at small calcification (AUC = 0.72, p < 0.001) and 679 at large calcification (AUC = 0.76, p = 0.001). Target lesions containing small calcification with maxLCBI4mm ≥ 585 more likely exhibited a greater CTFC (p < 0.001). In those with large calcification, 55.6% of them had maxLCBI4mm ≥ 400 [vs. 56.2% (small calcification), p = 0.82]. Furthermore, a higher CTFC (p < 0.001) was observed in association with maxLCBI4mm ≥ 679 at large calcification. On multivariable analysis, maxLCBI4mm at large calcification still independently predicted no-reflow phenomenon (OR = 1.60, 95%CI = 1.32–1.94, p < 0.001). MaxLCBI4mm at target lesions exhibiting large calcification elevated a risk of no-reflow phenomenon after PCI. Calcified plaque containing lipidic materials is not necessarily stable lesion, but could be active and high-risk one causing no-reflow phenomenon.

Ex-vivo atherosclerotic plaque characterization using spectral photon-counting CT: Comparing material quantification to histology

Background and aimsAtherosclerotic plaques are characterized as being vulnerable to rupture based on a series of histologically defined features, including a lipid-rich necrotic core, spotty calcification and ulceration. Existing imaging modalities have limitations in their ability to distinguish between different materials and structural features. We examined whether X-ray spectral photon-counting computer tomography (SPCCT) images were able to distinguish key plaque features in a surgically excised specimen from the carotid artery with comparison to histological images. MethodsAn excised carotid plaque was imaged in the diagnostic X-ray energy range of 30–120 keV using a small-bore SPCCT scanner equipped with a Medipix3RX photon-counting spectral X-ray detector with a cadmium telluride (CdTe) sensor. Material identification and quantification (MIQ) images of the carotid plaque were generated using proprietary MIQ software at 0.09 mm volumetric pixels (voxels). The plaque was sectioned, stained and photographed at high resolution for comparison. ResultsA lipid-rich core with spotty calcification was identified in the MIQ images and confirmed by histology. MIQ showed a core region containing lipid, with a mean concentration of 260 mg lipid/ml corresponding to a mean value of −22HU. MIQ showed calcified regions with mean concentration of 41 mg Ca/ml corresponded to a mean value of 123HU. An ulceration of the carotid wall at the bifurcation was identified to be lipid-lined, with a small calcification identified near the breach of the artery wall. ConclusionsSPCCT derived material identification and quantification images showed hallmarks of vulnerable plaque including a lipid-rich necrotic core, spotty calcifications and ulcerations.