Translating microcalcification biomarker information into the laboratory: A preliminary assessment utilizing core biopsies obtained from sites of mammographic calcification.

Rationale and objectives: The potential of breast microcalcification chemistry to provide clinically valuable intelligence is being increasingly studied. However, acquisition of crystallographic details has, to date, been limited to high brightness, synchrotron radiation sources. This study, for the first time, evaluates a laboratory-based system that interrogates histological sections containing microcalcifications. The principal objective was to determine the measurement precision of the laboratory system and assess whether this was sufficient to provide potentially clinical valuable information. Materials and methods: Sections from 5 histological specimens from breast core biopsies obtained to evaluate mammographic calcification were examined using a synchrotron source and a laboratory-based instrument. The samples were chosen to represent a significant proportion of the known breast tissue, mineralogical landscape. Data were subsequently analysed using conventional methods and microcalcification characteristics such as crystallographic phase, chemical deviation from ideal stoichiometry and microstructure were determined. Results: The crystallographic phase of each microcalcification (e.g., hydroxyapatite, whitlockite) was easily determined from the laboratory derived data even when a mixed phase was apparent. Lattice parameter values from the laboratory experiments agreed well with the corresponding synchrotron values and, critically, were determined to precisions that were significantly greater than required for potential clinical exploitation. Conclusion: It has been shown that crystallographic characteristics of microcalcifications can be determined in the laboratory with sufficient precision to have potential clinical value. The work will thus enable exploitation acceleration of these latent microcalcification features as current dependence upon access to limited synchrotron resources is minimized.

Microcalcification crystallography as a potential marker of DCIS recurrence.

Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation.

Exploration of utility of combined optical photothermal infrared and Raman imaging for investigating the chemical composition of microcalcifications in breast cancer.

Microcalcifications play an important role in cancer detection. They are evaluated by their radiological and histological characteristics but it is challenging to find a link between their morphology, their composition and the nature of a specific type of breast lesion. Whilst there are some mammographic features that are either typically benign or typically malignant often the appearances are indeterminate. Here, we explore a large range of vibrational spectroscopic and multiphoton imaging techniques in order to gain more information about the composition of the microcalcifications. For the first time, we validated the presence of carbonate ions in the microcalcifications by O-PTIR and Raman spectroscopy at the same time, the same location and the same high resolution (0.5 µm). Furthermore, the use of multiphoton imaging allowed us to create stimulated Raman histology (SRH) images which mimic histological images with all chemical information. In conclusion, we established a protocol for efficiently analysing the microcalcifications by iteratively refining the area of interest.

A multi-modal exploration of heterogeneous physico-chemical properties of DCIS breast microcalcifications.

Ductal carcinoma in situ (DCIS) is frequently associated with breast calcification. This study combines multiple analytical techniques to investigate the heterogeneity of these calcifications at the micrometre scale. X-ray diffraction, scanning electron microscopy and Raman and Fourier-transform infrared spectroscopy were used to determine the physicochemical and crystallographic properties of type II breast calcifications located in formalin fixed paraffin embedded DCIS breast tissue samples. Multiple calcium phosphate phases were identified across the calcifications, distributed in different patterns. Hydroxyapatite was the dominant mineral, with magnesium whitlockite found at the calcification edge. Amorphous calcium phosphate and octacalcium phosphate were also identified close to the calcification edge at the apparent mineral/matrix barrier. Crystallographic features of hydroxyapatite also varied across the calcifications, with higher crystallinity centrally, and highest carbonate substitution at the calcification edge. Protein was also differentially distributed across the calcification and the surrounding soft tissue, with collagen and ß-pleated protein features present to differing extents. Combination of analytical techniques in this study was essential to understand the heterogeneity of breast calcifications and how this may link crystallographic and physicochemical properties of calcifications to the surrounding tissue microenvironment.

COVID-19-Related Lung Parenchymal Uptake on 18F-PSMA-1007 PET/CT.

ABSTRACT: A 70-year-old man with newly diagnosed prostate cancer underwent 18F-PSMA-1007 PET/CT for staging. PSMA-avid primary prostatic malignancy was identified. Incidental intense patchy peripheral lung uptake was also noted. The patient tested positive for COVID-19 infection.

Screening detects a myriad of breast disease - refining practice will increase effectiveness and reduce harm.

For many individuals, the term 'cancer' equates to a disease that if untreated will progress, spread from the area initially affected and ultimately cause death. 'Breast cancer', however, is a diverse of range of pathological entities, incorporating indolent to fast-growing and aggressive lesions, with varying histological patterns, clinical presentations, treatment responses and outcomes. Screening for malignancy is based on the assumption that cancer has a gradual, orderly progression and that detecting lesions earlier in their natural history, and intervening, will reduce mortality. The natural history of epithelial atypia, ductal carcinoma in situ and even invasive breast cancer is poorly understood, but widely variable. We believe that population breast screening methodology needs to change to focus on diagnosis of lesions of greatest clinical relevance.

Calcification Microstructure Reflects Breast Tissue Microenvironment.

Microcalcifications are important diagnostic indicators of disease in breast tissue. Tissue microenvironments differ in many aspects between normal and cancerous cells, notably extracellular pH and glycolytic respiration. Hydroxyapatite microcalcification microstructure is also found to differ between tissue pathologies, including differential ion substitutions and the presence of additional crystallographic phases. Distinguishing between tissue pathologies at an early stage is essential to improve patient experience and diagnostic accuracy, leading to better disease outcome. This study explores the hypothesis that microenvironment features may become immortalised within calcification crystallite characteristics thus becoming indicators of tissue pathology. In total, 55 breast calcifications incorporating 3 tissue pathologies (benign - B2, ductal carcinoma in-situ - B5a and invasive malignancy - B5b) from archive formalin-fixed paraffin-embedded core needle breast biopsies were analysed using X-ray diffraction. Crystallite size and strain were determined from 548 diffractograms using Williamson-Hall analysis. There was an increased crystallinity of hydroxyapatite with tissue malignancy compared to benign tissue. Coherence length was significantly correlated with pathology grade in all basis crystallographic directions (P < 0.01), with a greater difference between benign and in situ disease compared to in-situ disease and invasive malignancy. Crystallite size and non-uniform strain contributed to peak broadening in all three pathologies. Furthermore, crystallite size and non-uniform strain normal to the basal planes increased significantly with malignancy (P < 0.05). Our findings support the view that tissue microenvironments can influence differing formation mechanisms of hydroxyapatite through acidic precursors, leading to differential substitution of carbonate into the hydroxide and phosphate sites, causing significant changes in crystallite size and non-uniform strain.

18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma.

PURPOSE: The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. PATIENTS AND METHODS: F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan-Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. RESULTS: PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan-Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. CONCLUSIONS: F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

Has integrated 18F FDG PET/CT improved staging, reduced early recurrence or increased survival in oesophageal cancer?

BACKGROUND: Survival in oesophageal cancer remains poor with high post-operative recurrence rates. PET/CT was introduced to the Three-Counties Cancer Network (3CCN) in 2006 to detect 'occult' metastatic disease not seen with conventional staging modalities. This study aims to determine whether the introduction of Integrated fluorodeoxyglucose (18F) Positron Emission Tomography (PET/CT) has changed the management, improved survival or reduced the rate of early post-operative recurrence in patients with operable oesophageal cancer. METHODS: A retrospective review was undertaken of all patients diagnosed with oesophageal cancer in the 3CCN from 2005 to 2009. Early recurrence was defined as proven recurrence locally or at a distant site within one year of resection. RESULTS: 725 patients were identified. 200 (27.6%) patients underwent staging PET/CT. PET/CT altered treatment intent in 19 (9.5%) patients. 128 (17.7%) patients underwent oesophageal resection, 90 (70.3%) of which had a staging PET/CT. No significant difference was noted in post-operative mortality (4.4% Vs 5.3%, p = 0.8) or early recurrence where PET/CT was performed when adjusted for age, sex, stage or neo-adjuvant chemotherapy (p = 0.761, OR 1.136[95% CI 0.499-2.585]). PET/CT had no significant effect on survival (log-rank test; Chi-square 0.710, p = 0.4). CONCLUSION: PET/CT has improved the accuracy of oesophageal cancer staging avoiding potentially unnecessary surgery. Ultimately however, its use has had no effect on early recurrence or survival rates. Inaccurate identification of occult metastatic disease prior to the introduction of staging PET/CT does not appear to be the primary cause of early recurrence in patients with oesophageal cancer.

False positive diagnosis of malignancy in a case of cryptogenic organising pneumonia presenting as a pulmonary mass with mediastinal nodes detected on fluorodeoxyglucose-positron emission tomography: a case report.

INTRODUCTION: We report the case of a patient with positive findings on a lung emission tomography/computed tomography (PET/CT) scan, with possible contra lateral mediastinal involvement, which strongly suggested an inoperable lung carcinoma. The lung mass proved to be a cryptogenic organising pneumonia. While the latter has previously been shown to be PET/CT positive, mediastinal involvement simulating malignant spread has not been previously reported. CASE PRESENTATION: A 50-year-old Caucasian woman presented with a history of unproductive cough and was found to have a mass in the right upper lobe as shown on chest X-ray and a computed tomography scan. A subsequent PET/CT scan showed strong uptake in the right upper lobe (maximum standard uptake values (SUVmax) 9.6) with increased uptake in the adjacent mediastinum and contralateral mediastinal nodes. Surgical resection and mediastinoscopy revealed cryptogenic organising pneumonia, with enlarged reactive mediastinal lymph nodes. CONCLUSION: The case illustrates the limits of PET/CT scanning as a diagnostic tool, and emphasizes the importance of obtaining histological confirmation of malignant diseases whenever possible.

Computed tomography of acute small bowel obstruction: pictorial essay.

In many patients, the diagnosis of SBO can often be made by a combination of clinical history, physical examination and plain radiographs. However, in many cases, the diagnosis of SBO may be difficult. Abdominal radiographs are limited in their ability to diagnose SBO and, more particularly, to identify a specific underlying cause. Although barium studies, ultrasonography and magnetic resonance imaging may all play a role in the evaluation of SBO, CT should be the examination of choice for most patients when the diagnosis and underlying cause of SBO is unclear. It may help differentiate pseudo-obstruction from true obstruction, and a specific underlying cause can often be determined. Signs of closed-loop obstruction, strangulation, perforation or infarction may be detected and allow for more timely and appropriate surgical management. We advocate the use of CT in any patient with SBO where the cause or diagnosis is unclear. We have attempted to demonstrate a range of clinical cases in our practice where CT played an invaluable role in the evaluation of our patients.

Comminuted fracture of the ulnar sesamoid of the metacarpophalangeal joint of the thumb: an uncommon injury.

Fracture of the ulnar sesamoid of the metacarpophalangeal joint of the thumb is rare. Injury may be caused as a result of hyperextension or, less frequently, direct trauma. A sesamoid may be incompletely ossified, making it difficult to diagnose the fracture on radiographs. Early recognition of this entity leads to appropriate management. The case of a 26-year-old man who sustained a hyperextension injury of the thumb is presented. Radiographs demonstrated a fracture of the ulnar sesamoid of the thumb metacarpophalangeal joint. The literature regarding this uncommon injury is discussed.

Emergency radiology in Canada: a national survey.

OBJECTIVE: To document the existing radiology services available to emergency physicians in hospitals across Canada and to preview future trends and needs. METHODS: Questionnaires (n = 130) regarding the type, availability and satisfaction with radiology services were distributed to radiologists and emergency physicians at 65 hospitals across Canada. RESULTS: Fifty-three (41%) questionnaires were returned, and 45 (35%) completed questionnaires from 35 hospitals were used for analysis (24 from radiologists and 21 from emergency physicians). Plain radiographs were available in all hospitals at all times. Ultrasonography, intravenous pyleograms and computed tomography (CT) were available in all departments during normal working hours; after hours, CT was unavailable in 1 hospital and ultrasonography was unavailable in 2. Focused assessment with sonography for trauma (FAST) was routinely performed for blunt abdominal trauma in 6 centres, and 10 centres had teleradiology services. Regarding the quality of emergency service, 7 of 45 responded "poor," 4 "average," 14 "good," and 17 of 45 rated service "excellent." Interestingly, most radiologists answered "good" or "excellent," and most of the "poor" responses came from emergency physicians. Regarding staff coverage after 5 pm, 34 hospitals provided CT services, 20 had ultrasonography staff available, and there was radiology nursing coverage in 14 hospitals. Clinical details on requisitions were generally rated "adequate" or "poor." Although most radiograph reports were available within 48 hours, some took longer. Hot-seat reporting was available in 11 centres. During normal working hours, radiologists were the first to read films in 5 of 35 hospitals. After hours, emergency physicians were the first to read films in all hospitals, but only 14 hospitals indicated they were "formally" trained to do so. CONCLUSION: This survey documents the strengths and weaknesses of the radiology services available to emergency physicians. The perceptions of emergency physicians and radiologists of the adequacy those services differ significantly.

Unenhanced helical CT in the investigation of acute flank pain.

Unenhanced helical CT has emerged as the imaging technique of choice for the investigation of patients presenting with acute flank pain and suspected nephroureteric stone disease. There are several signs identifiable on unenhanced CT that support a diagnosis of stone disease. However, there are many pitfalls, that may confound a correct diagnosis. Some of the common pitfalls, together with methods to avoid such occurrences, will be discussed. A review of some of the common alternative diagnoses that may mimic the symptoms of nephroureteric stone disease is illustrated.