Preoperative staging by multimodal imaging in newly diagnosed breast cancer: Diagnostic performance of contrast-enhanced spectral mammography compared to conventional mammography, ultrasound, and MRI.

PURPOSE: To compare contrast-enhanced spectral mammography (CESM) with mammography (Mx), ultrasound (US), and magnetic resonance imaging (MRI) regarding breast cancer detection rate and preoperative local staging. MATERIAL AND METHODS: This prospective observational, single-centre study included 128 female patients (mean age 55.8 ± 11.5 years) with a newly diagnosed malignant breast tumour during routine US and Mx were prospectively enrolled. CESM and MRI examinations were performed within the study. Analysis included interreader agreement, tumour type and grade distribution, detection rates (DR), imaging morphology, contrast-enhancement and was performed by two independent readers blinded to patient history and histopathological diagnosis. Assessment of local disease extent was compared between modalities via Bland-Altman plots. RESULTS: One-hundred-and-ten tumours were classified as NST (85.9%), 4 as ILC (3.1%) and 10 as DCIS (7.8%). DR was highest for MRI (128/128, 100.0%), followed by US (124/128, 96.9%) and CESM (123/128, 96.1%) and lowest for conventional Mx (106/128, 82.8%) (p = 0.0002). Higher breast density did not negatively affect DR of US, CESM or MRI. Local tumour extent measurements based on CESM (Bland-Altman bias 6.6, standard deviation 30.2) showed comparable estimation results to MRI, surpassing Mx (23.4/43.7) and US (35.4/40.5). Even though detection of multifocality and multicentricity was highest for CESM and MRI (p < 0.0001), second-look rates, i.e., targeted US examinations after MRI or CESM, were significantly lower for CESM (10.2% of cases) compared to MRI (16.2%) with a significantly higher true positive rate for CESM (72.0%) vs. MRI (42.5%). CONCLUSION: CESM is a viable alternative to MRI for lesion detection and local staging in newly diagnosed malignant breast cancer and provides higher specificity in regard to second-look examinations.

Interval breast cancer: Analysis of occurrence, subtypes and implications for breast cancer screening in a model region.

PURPOSE: Interval breast carcinomas (IBC) constitute a subgroup of malignancies in women participating in a breast cancer screening programme, yet diagnosed outside of a screening appointment. Tyrol is an Austrian screening model region with a dedicated IBC board. We analysed IBC subtype distribution, demographic and biological parameters and implications for screening programmes. METHOD: 161 patients with an IBC diagnosed from 2014 to 2017 were retrospectively analysed and grouped into true, occult, minimal-signs, and false negative (due to reading or technical error) IBCs cases by three independent readers. The influence of demographic and disease-related covariates were assessed. RESULTS: The median interval from screening to diagnostic diagnosis was 12.8 months (range 1.1 to 23.9 months). Most cases were true (36.02%), occult (31.06%) and false-negative IBCs due to reading errors (29.81%). Interobserver agreement was rated as 'high' between all readers. Higher breast density was associated with true and occult IBCs. The rate of invasive subtypes was highest in true IBCs. Regardless of smaller tumour size in true and occult IBCs, doubling time was lower and ki-67 index higher in true and occult compared to false-negative IBCs. CONCLUSIONS: True and occult IBCs present with a more aggressive biological phenotype and are associated with younger age and higher breast density. Additional yearly ultrasound examinations in women at risk may aid in the earlier detection.

Dual-energy contrast-enhanced spectral mammography (CESM).

Dual-energy contrast-enhanced mammography is one of the latest developments in breast care. Imaging with contrast agents in breast cancer was already known from previous magnetic resonance imaging and computed tomography studies. However, high costs, limited availability-or high radiation dose-led to the development of contrast-enhanced spectral mammography (CESM). We reviewed the current literature, present our experience, discuss the advantages and drawbacks of CESM and look at the future of this innovative technique.

A longitudinal VBM study monitoring treatment with erythropoietin in patients with Friedreich ataxia.

BACKGROUND: Recombinant human erythropoietin (rhuEPO) has received considerable attention because of its neuroprotective properties. It has recently been reported that rhuEPO increases frataxin levels in combination with clinical improvement in rhuEPO treated patients with Friedreich ataxia (FRDA). PURPOSE: To determine possible therapy dependent intracranial volume changes after treatment with rhuEPO using voxel-based morphometry (VBM). MATERIAL AND METHODS: Nine FRDA patients were scanned on the same 1.5-Tesla MRI scanner before and after treatment with rhuEPO. FRDA patients received 5000 IU rhuEPO thrice weekly subcutaneously for a time period of 8 weeks followed by 2000 IU thrice weekly over 6 months. To test for re-test reliability a control group of 12 healthy volunteers were scanned twice on the same scanner without rhuEPO treatment. Neurological state was defined by the Friedreich Ataxia Rating Scale (FARS) and the Scale for the Assessment and Rating of Ataxia (SARA). Statistical parametric mapping software was used for image processing and statistical analysis. RESULTS: When comparing follow-up scans after rhuEPO treatment with baseline scans (P <0.001 uncorrected) an increase of gray matter volume was observed bilaterally in the Pulvinar and the posterior parietal cortex. Moreover, clinical improvement detected using specific Ataxia scores correlated with VBM results in the pulvinar. CONCLUSION: Given the limitation of a small sample size, our study confirms previous findings that MRI may serve as reliable biomarker in neurodegenerative diseases as well as in monitoring of microstructural changes representing disease progression and/or therapy effects.

Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis.

BACKGROUND: Elevated plasma fibrinogen levels are a well known finding in acute infectious diseases, acute stroke and myocardial infarction. However its role in the cerebrospinal fluid (CSF) of acute and chronic central (CNS) and peripheral nervous system (PNS) diseases is unclear. FINDINGS: We analyzed CSF and plasma fibrinogen levels together with routine parameters in patients with multiple sclerosis (MS), acute inflammatory diseases of the CNS (bacterial and viral meningoencephalitis, BM and VM) and PNS (Guillain-Barré syndrome; GBS), as well as in non-inflammatory neurological controls (OND) in a total of 103 patients. Additionally, MS patients underwent cerebral MRI scans at time of lumbar puncture.CSF and plasma fibrinogen levels were significantly lower in patients with MS and OND patients as compared to patients with BM, VM and GBS. There was a close correlation between fibrinogen levels and albumin quotient (rho = 0.769, p < 0.001) which strongly suggests passive transfer of fibrinogen through the blood-CSF-barrier during acute inflammation. Hence, in MS, the prototype of chronic neuroinflammation, CSF fibrinogen levels were not elevated and could not be correlated to clinical and neuroradiological outcome parameters. CONCLUSIONS: Although previous work has shown clear evidence of the involvement of fibrinogen in MS pathogenesis, this is not accompanied by increased fibrinogen in the CSF compartment.

Functional imaging in phaeochromocytoma and neuroblastoma with 68Ga-DOTA-Tyr 3-octreotide positron emission tomography and 123I-metaiodobenzylguanidine.

PURPOSE: (68)Ga-DOTA-Tyr(3)-octreotide positron emission tomography ((68)Ga-DOTA-TOC PET) has proven to be superior to (111)In-DTPA-D-Phe(1)-octreotide ((111)In-octreotide) planar scintigraphy and SPECT imaging in neuroendocrine tumours (NETs). Because of these promising results, we compared the accuracy of (123)I-metaiodobenzylguanidine ((123)I-MIBG) imaging with PET in the diagnosis and staging of metastatic phaeochromocytoma and neuroblastoma, referring to radiological imaging as reference standard. METHODS: Three male and eight female patients (age range 3 to 68 years) with biochemically and histologically proven disease were included in this study. Three male and three female patients were suffering from phaeochromocytoma, and five female patients from neuroblastoma. Comparative evaluation included morphological imaging with CT or MRI, functional imaging with (68)Ga-DOTA-TOC PET and (123)I-MIBG imaging. Imaging results were analysed on a per-patient and on a per-lesion basis. RESULTS: On a per-patient basis, both (68)Ga-DOTA-TOC and (123)I-MIBG showed a sensitivity of 100%, when compared with anatomical imaging. In phaeochromocytoma patients, on a per-lesion basis, the sensitivity of (68)Ga-DOTA-TOC was 91.7% and that of (123)I-MIBG was 63.3%. In neuroblastoma patients, on a per-lesion basis, the sensitivity of (68)Ga-DOTA-TOC was 97.2% and that of (123)I-MIBG was 90.7%. Overall, in this patient cohort, (68)Ga-DOTA-TOC PET identified 257 lesions, anatomical imaging identified 216 lesions, and (123)I-MIBG identified only 184 lesions. In this patient group, the overall sensitivity of (68)Ga-DOTA-TOC PET on a lesion basis was 94.4% (McNemar p<0.0001) and that of (123)I-MIBG was 76.9% (McNemar p<0.0001). CONCLUSION: Our analysis in this relatively small patient cohort indicates that (68)Ga-DOTA-TOC PET may be superior to (123)I-MIBG gamma-scintigraphy and even to the reference CT/MRI technique in providing particularly valuable information for pretherapeutic staging of phaeochromocytoma and neuroblastoma.

Serum levels of ischemia-modified albumin in healthy volunteers after exercise-induced calf-muscle ischemia.

BACKGROUND: Ischemia-modified albumin (IMA) is an emerging marker of ischemia. To investigate the applicability of IMA for the diagnosis of skeletal muscle ischemia, we examined IMA changes as measured by the albumin-cobalt binding test, in a group of healthy volunteers after standardized exercise-induced calf muscle ischemia. METHODS: A total of 12 healthy volunteers underwent standardized exercise on a plantar flexion pedal. Ischemic conditions were achieved by inflating a femoral blood pressure cuff at incremental pressures of 0, 60, 90, 120 and 150 mm Hg. Calf muscle ischemia was identified by synchronous 31P magnetic resonance spectroscopy, measuring intracellular concentrations of phosphocreatine (PCr) and inorganic phosphate (Pi). In addition, IMA, serum albumin, lactate, troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at baseline and at 5, 10, 30, 360 and 720 min after cuff release. RESULTS: Magnetic resonance spectroscopy showed calf muscle ischemia in all participants upon exercise and cuff inflation. Circulating IMA concentrations increased significantly after cuff release (p=0.03) and returned to baseline within 30 min. While we found a significant negative correlation with albumin, there was no association of IMA levels with lactate or intracellular levels of PCr or Pi in samples obtained at baseline and post-ischemia. TnT and NT-proBNP remained within the normal range throughout the observation period in all participants. CONCLUSIONS: IMA may represent a clinical marker for skeletal muscle ischemia, although its lack of specificity requires careful clinical interpretation of data. The short period of IMA elevation after ischemic exercise requires standardized conditions for use as a diagnostic tool and hints at IMA applicability as a marker of prolonged or chronic ischemia.

High-energy phosphate metabolism during calf ergometry in patients with isolated aorto-iliac artery stenoses.

OBJECTIVES: Patients with peripheral arterial disease (PAD) and aorto-iliac atherosclerotic lesions suffer from a broad range of complaints, such as pain at the hip, the thigh, and calf claudication. The purpose of this study was to investigate the high-energy metabolism in the calf muscle of patients with PAD with isolated aorto-iliac stenoses during incremental plantar flexion exercise. MATERIALS AND METHODS: Using a 1.5 T whole-body magnetic resonance (MR) scanner, 12 patients with PAD with uni- or bilateral aorto-iliac atherosclerotic lesions and 10 healthy male controls underwent serial phosphor-31 MR spectroscopy during incremental exercise at 2, 3, 4, and 5 W. The phosphocreatine (PCr) time constants were calculated for each increment and recovery using a monoexponential model. In the patient group, the run-off resistance was determined on MR angiograms. In both the patients and the controls, the ankle brachial pressure index was measured. RESULTS: The diseased legs exhibited significantly increased PCr time constants during the second and the third workload increment at 3 and 4 W, but not during the first increment at 2 W and recovery compared with normal controls. Only 3 diseased legs succeeded the last increment at 5 W. We detected significant correlations between the ankle brachial pressure index scores and the PCr time constants when including both the diseased and the control legs. The diseased legs showed a significant correlation with the run-off resistance only during the first increment. CONCLUSIONS: Our study shows that the impairment of muscle metabolism, expressed by prolonged PCr time constants, occurs with greater work intensities in patients with aorto-iliac disease compared with patients with multisegmental PAD, as recently published, whereas our patients collective exhibited normal PCr recovery time constants. Our findings may help to understand variability of clinical symptoms in aorto-iliac PAD.

High-energy phosphate metabolism in the calf muscle during moderate isotonic exercise under different degrees of cuff compression: a phosphorus 31 magnetic resonance spectroscopy study.

BACKGROUND: The purpose of this study was to investigate phosphocreatine (PCr) and inorganic phosphate levels as well as pH changes in exercising muscle at a workload of 4.5 W under progressive cuff stenoses, whereby the flow reduction due to cuff compression was quantified by flow-sensitive magnetic resonance imaging. METHODS: By using a whole-body 1.5-T magnetic resonance scanner and an exercise bench, serial phosphorus 31 (31P) magnetic resonance spectroscopy with a time resolution of 30 seconds was performed in 10 healthy men. Percentage changes in PCr, inorganic phosphate (Pi), and pH were statistically evaluated in comparison with baseline. The exercise protocol was characterized by a constant workload level of 4.5 W. Ischemic conditions were achieved by a cuff that was placed at the upper leg. Consecutively, increments of 0, 60, 90, 120, and 150 mm Hg were applied. Each increment lasted for 3 minutes. The following rest period was 10 minutes. RESULTS: Blood flow increased significantly immediately after the onset of muscle exercise. No significant changes in blood flow were detected as long as the air pressure of the pneumatic cuff was 60 to 90 mm Hg. Significant reductions in blood flow were observed immediately after inflation of the cuff to 120 and 150 mm Hg. PCr passed into a steady state during the first increment with 0 mm Hg and showed no substantial changes during the increment with 60, 90, and 120 mm Hg. PCr hydrolysis seemed progressive during the 150-mm Hg increment. Pi passed into a plateau level at the onset of exercise and increased significantly at the increment of 150 mm Hg. The pH turned into a steady state with no significant changes during the increments up to 120 mm Hg. At 150 mm Hg, pH decreased progressively. PCr levels at the end of the 150-mm Hg increment correlated significantly and moderately with the reduction in blood flow. CONCLUSIONS: Our study shows that the ischemic condition during constant muscle exercise is clearly characterized by PCr and Pi kinetics, as well as by pH changes. The correlation between the degree of blood flow reduction and PCr levels in the exercising muscle groups, which are supplied by the stenosed arteries, is the first essential of using 31P magnetic resonance spectroscopy in the assessment of the effect of arterial stenoses on muscle function in claudicants.