Combined Brain-Heart Imaging in Takotsubo Syndrome: Towards a Holistic Patient Assessment.

Takotsubo syndrome (TTS) is a type of cardiomyopathy usually precipitated by either emotional or physical stress and potentially leading to reversible heart failure. There is emerging evidence indicating an interaction between the brain and the heart in patients with TTS. Nevertheless, these new insights are not reflected in the current clinical approach to TTS. The application of novel and existing imaging modalities for the evaluation of brain-heart interactions is an interesting approach that could potentially augment diagnostic and prognostic yield, as well as improve our pathophysiologic understanding in the context of TTS. In this opinion piece, we discuss the evidence supporting a brain-heart interaction in patients with TTS and discuss how a combined evaluation of brain-heart interactions could potentially be implemented.

Multiparametric Cardiac Magnetic Resonance Assessment in Sickle Beta Thalassemia.

Cardiac involvement in sickle beta thalassemia (Sß-thal) patients has been poorly investigated. We aimed to evaluate cardiac function and myocardial iron overload by cardiovascular magnetic resonance (CMR) in patients with Sß-thal. One-hundred and eleven Sß-thal patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network were studied and compared with 46 sickle cell anemia (SCA) patients and with 111 gender- and age- matched healthy volunteers. Cine images were acquired to quantify biventricular function. Myocardial iron overload (MIO) was assessed by the T2* technique, while macroscopic myocardial fibrosis was evaluated by the late gadolinium enhancement (LGE) technique. In Sß-thal and SCA patients, the morphological and functional CMR parameters were not significantly different, except for the left atrial area and left ventricular (LV) stroke volume, indexed by body surface area (p = 0.023 and p = 0.048, respectively), which were significantly higher in SCA patients. No significant differences between the two groups were found in terms of myocardial iron overload and macroscopic myocardial fibrosis. When compared to healthy subjects, Sß-thal patients showed significantly higher bi-atrial and biventricular parameters, except for LV ejection fraction, which was significantly lower. The CMR analysis confirmed that Sß-thal and SCA patients are phenotypically similar. Since Sß-thal patients showed markedly different morphological and functional indices from healthy subjects, it would be useful to identify Sß-thal/SCA-specific bi-atrial and biventricular reference values.

Impact of the COVID-19 Pandemic on Iron Overload Assessment by MRI in Patients with Hemoglobinopathies: The E-MIOT Network Experience.

BACKGROUND: The E-MIOT (Extension-Myocardial Iron Overload in Thalassemia) project is an Italian Network assuring high-quality quantification of tissue iron overload by magnetic resonance imaging (MRI). We evaluated the impact of the COVID-19 pandemic on E-MIOT services. METHODS: The activity of the E-MIOT Network MRI centers in the year 2020 was compared with that of 2019. A survey evaluated whether the availability of MRI slots for patients with hemoglobinopathies was reduced and why. RESULTS: The total number of MRI scans was 656 in 2019 and 350 in 2020, with an overall decline of 46.4% (first MRI: 71.7%, follow-up MRI: 36.9%), a marked decline (86.9%) in the period March-June 2020, and a reduction in the gap between the two years in the period July-September. A new drop (41.4%) was recorded in the period October-December for two centers, due to the general reduction in the total amount of MRIs/day for sanitization procedures. In some centers, patients refused MRI scans for fear of getting COVID. Drops in the MRI services >80% were found for patients coming from a region without an active MRI site. CONCLUSIONS: The COVID-19 pandemic had a strong negative impact on MRI multi-organ iron quantification, with a worsening in the management of patients with hemoglobinopathies.

Tumor Diagnosis and Treatment: Imaging Assessment.

At present, oncologic imaging is crucial for clinical decision-making [...].

Sternal transplant using cadaveric allograft: quantitative and qualitative assessment of bone healing by computed tomography.

BACKGROUND: Sternal transplant using cadaveric allograft (STCA) is a complex and rarely performed surgical procedure usually applied for massive bone tissue loss, sternotomy complications, or neoplastic resections. Although radiological imaging and especially computed tomography (CT) is routinely applied for the post-surgical assessment, up to now, a standardized approach evaluating the outcome of STCAs is missing. Therefore, aim of this study was to qualitatively and quantitatively evaluate, by CT, bone healing after STCA. METHODS: The first and the last available postsurgical CT of patients who underwent STCA in two tertiary centers between 2009 and 2017 were collected. Standardized regions of interest were applied on the cancellous bone along the transplanted sternum, and, as reference, on the fourth thoracic vertebra, at both time points, collecting the density values. The areas nearby the fixation devices were assessed by a four-points qualitative score. To evaluate the mineralization, the analysis of the variance (ANOVA) with post-hoc Bonferroni correction was applied for the quantitative measurements while the Wilcoxon test was used for the qualitative score (P<0.05). To evaluate the intra-rater reliability of the qualitative and the quantitative analyses, the same rater repeated the measurements after two months and the Cohen's kappa (k) and the intraclass correlation coefficient (ICC) were computed. RESULTS: Fourteen patients (11 females, 61±12.8 years) were examined. The first control CTs were performed 32±40.26 days after the STCA and the last CT were acquired after 729±745 days. The quantitative and the qualitative score significantly increased between the two intervals (P<0.05, each). The density of the transplanted sternum was lower than that of the vertebral reference at the first CT (P=0.006) while no differences occurred at the last control (P=0.361). The assessments showed high intra-rater reliability and agreement (ICC ≥0.890, k≥0.906). CONCLUSIONS: The hereby-proposed qualitative and quantitative methods demonstrated to be good tools for assessing bone healing after STCA.

Subtyping of Primary Aldosteronism in the AVIS-2 Study: Assessment of Selectivity and Lateralization.

CONTEXT: Adrenal venous sampling (AVS) is the key test for subtyping primary aldosteronism (PA), but its interpretation varies widely across referral centers and this can adversely affect the management of PA patients. OBJECTIVES: To investigate in a real-life study the rate of bilateral success and identification of unilateral aldosteronism and their impact on blood pressure outcomes in PA subtyped by AVS. DESIGN AND SETTINGS: In a retrospective analysis of the largest international registry of individual AVS data (AVIS-2 study), we investigated how different cut-off values of the selectivity index (SI) and lateralization index (LI) affected rate of bilateral success, identification of unilateral aldosteronism, and blood pressure outcomes. RESULTS: AVIS-2 recruited 1625 individual AVS studies performed between 2000 and 2015 in 19 tertiary referral centers. Under unstimulated conditions, the rate of biochemically confirmed bilateral AVS success progressively decreased with increasing SI cut-offs; furthermore, with currently used LI cut-offs, the rate of identified unilateral PA leading to adrenalectomy was as low as <25%. A within-patient pairwise comparison of 402 AVS performed both under unstimulated and cosyntropin-stimulated conditions showed that cosyntropin increased the confirmed rate of bilateral selectivity for SI cut-offs ≥ 2.0, but reduced lateralization rates (P < 0.001). Post-adrenalectomy outcomes were not improved by use of cosyntropin or more restrictive diagnostic criteria. CONCLUSION: Commonly used SI and LI cut-offs are associated with disappointingly low rates of biochemically defined AVS success and identified unilateral PA. Evidence-based protocols entailing less restrictive interpretative cut-offs might optimize the clinical use of this costly and invasive test. (J Clin Endocrinol Metab XX: 0-0, 2020).

Impact of gadolinium-based contrast agent in the assessment of Crohn's disease activity: Is contrast agent injection necessary?

PURPOSE: To determine whether magnetic resonance enterography (MRE) performed without intravenous contrast injection is diagnostically noninferior to conventional contrast-enhanced MRE (CE-MRE) in patients with Crohn's disease (CD). MATERIALS AND METHODS: This was an Institutional Review Board (IRB)-approved retrospective study. Ninety-six patients (52 male and 44 female; 47.18 years ± 13.6) with a diagnosis of CD underwent MRE at 1.5T including T2 -weighted single-shot turbo-spin-echo, T2 -weighted spectral fat presaturation with inversion recovery (SPAIR), T1 -weighted balanced fast-field-echo MR sequences, and CE-MRE consisting in T1 -weighted breath-hold THRIVE 3D MRI sequences after administration of gadobenate dimeglumine (0.2 mL/kg of body weight). Unenhanced MRE, CE-MRE, and unenhanced MRE plus CE-MRE were reviewed in separate sessions with blinding by two readers in consensus, and subsequently by two other readers independently considering a subgroup of 20 patients. Crohn's Disease Endoscopic Index of Severity (CDEIS) and/or histologic analysis of the surgical specimen were considered as reference standards for the assessment of inflammatory activity. RESULTS: Patients revealed prevalently active (n = 55 patients) or quiescent CD (n = 41 patients). The agreement between unenhanced MRE vs. CE-MRE in interpreting active bowel inflammation was 96% (123/128 bowel segments; one-sided 95% confidence interval [CI], >94.4%). Unenhanced MRE vs. CE-MRE vs. unenhanced MRE plus CE-MRE revealed a diagnostic accuracy of 93% [90/96] vs. 92% [88/96] vs. 97% [93/96] (P > 0.05) in the diagnosis of active CD. Interreader agreement was very good for all variables (κ value = 0.8-0.9) except for the measurement of the length of disease (κ value = 0.45). CONCLUSION: Unenhanced MRE was noninferior to CE-MRE in diagnosing active inflammation in patients with CD.

Activity-based cost analysis of contrast-enhanced ultrasonography (CEUS) related to the diagnostic impact in focal liver lesion characterisation.

PURPOSE: This study was done to assess the clinical-diagnostic impact and cost of contrast-enhanced ultrasound (CEUS) versus computed tomography (CT) and magnetic resonance (MR) imaging in the characterisation of focal liver lesions. MATERIALS AND METHODS: CEUS with sulphur hexafluoride-filled microbubbles (SonoVue bolus 2.4 ml) was performed in 157 patients with 160 focal liver lesions identified by other diagnostic techniques. CEUS images were obtained during the arterial (15 to 35 s from contrast injection), portal venous (40 to 70 s) and late phase (up to 300 s from microbubble injection). Contrast-enhanced CT was performed with a 64-row multidetector CT. MRI was performed before and after administration of the liver-specific contrast agent gadobenate dimeglumine (Gd-BOPTA). A patient-by-patient activity-based cost analysis was performed. RESULTS: CEUS led to a change in the diagnostic workup in 131/157 patients (83.4 %) and in the therapeutic workup in 93/157 patients (59.2 %). CEUS allowed for the final diagnosis to be established in 133/157 patients (84.7 %). The full cost of CEUS was lower than that of contrast-enhanced CT and MR imaging. CONCLUSIONS: CEUS determined a change in the diagnostic and therapeutic workup in the characterisation of focal liver lesions and reduced the full costs of the diagnostic process. MAIN MESSAGES: • CEUS allows a correct diagnosis in more than 80 % of focal liver lesions. • CEUS has a significant impact on the diagnosis of focal liver lesions. • CEUS examination of focal liver lesions reduces total costs. • Dynamic MR with hepato-specific contrast medium remains the reference standard for lesion characterisation. • CEUS is low-cost, versatile and accurate in the characterisation of focal liver lesions.

Indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced computed tomography: assessment of the additional diagnostic value of contrast-enhanced ultrasound in the non-cirrhotic liver.

OBJECTIVE: To assess the additional diagnostic value of contrast-enhanced ultrasound (CEUS) in the characterization of indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced computed tomography (CT). METHODS: Fifty-five solid hepatic lesions (1-4 cm in diameter) in 46 non-cirrhotic patients (26 female, 20 male; age±SD, 55±10 years) underwent CEUS after being detected on contrast-enhanced CT which was considered as non-diagnostic after on-site analysis. Two blinded independent readers assessed CT and CEUS scans and were asked to classify retrospectively each lesion as a malignant or benign based on reference diagnostic criteria for the different hepatic lesion histotypes. Diagnostic accuracy and confidence (area--Az--under ROC curve) were assessed by using gadobenate dimeglumine-enhanced magnetic resonance (MR) imaging (n=30 lesions), histology (n=7 lesions), or US follow-up (n=18 lesions) as the reference standards. RESULTS: Final diagnoses included 29 hemangiomas, 3 focal nodular hyperplasias, 1 hepatocellular adenoma, and 22 metastases. The additional review of CEUS after CT images improved significantly (P<.05) the diagnostic accuracy (before vs after CEUS review=49% [20/55] vs 89% [49/55]--reader 1 and 43% [24/55] vs 92% [51/55]--reader 2) and confidence (Az, 95% Confidence Intervals before vs after CEUS review=.773 [.652-.895] vs .997 [.987-1]--reader 1 and .831 [.724-.938] vs .998 [.992-1]--reader 2). CONCLUSIONS: CEUS improved the characterization of indeterminate solid hepatic lesions identified on non-diagnostic contrast-enhanced CT by identifying some specific contrast enhancement patterns.

Diffusion-weighted magnetic resonance imaging in the prediction and assessment of chemotherapy outcome in liver metastases.

PURPOSE: This study assessed the capability of magnetic resonance (MR) diffusion-weighted imaging (DwI) with measurement of apparent diffusion coefficient (ADC) in both predicting and evaluating the response to chemotherapy (CHT) of liver metastases by itself and along with preliminary dimensional assessment. METHODS AND MATERIALS: Patients affected by liver metastases from cancers of the digestive tract and breast were prospectively enrolled and underwent computed tomography and MR-DwI before CHT (time 0) and 20-25 days after the beginning of the second cycle (time 3). Moreover, MR-DwI was performed 10-15 (time 1) and 20-25 days (time 2) after the beginning of the first cycle. Maximum diameter and mean ADC value (×10(-3) mm(2)/s) of metastases were evaluated. Lesions were classified as progressive disease (PD), stable disease (SD) or partial response (PR) according to dimensional changes between time 0 and time 3, following RECIST 1.1 indications. Clinically, PD lesions were defined as nonresponding (NR), and SD and PR lesions as responding (R). Analysis of variance and ROC analyses were performed (significance at p < 0.05). RESULTS: Eighty-six metastases (33 patients) were classified as follows: 15 PD, 39 SD and 32 PR without significant differences in mean ADC values among the groups before CHT and at all corresponding times. The mean ADC values of SD and PR groups at times 1 (respectively 1.66 ± 0.36 and 1.59 ± 0.23), 2 (1.72 ± 0.42 and 1.68 ± 0.37) and 3 (1.86 ± 0.44 and 1.73 ± 0.39) were significantly higher than the corresponding values at time 0 (1.50 ± 0.30 and 1.39 ± 0.33). An accurate cutoff value of ADC increase or diameter decrease for the early identification of R or NR lesions was not found. CONCLUSION: The pretreatment ADC value of a liver metastasis does not seem useful in predicting the CHT outcome. A trend towards early ADC increase, alone or occurring with dimensional decrease, may be a good indicator of a responding lesion.

Diagnostic imaging costs before and after digital tomosynthesis implementation in patient management after detection of suspected thoracic lesions on chest radiography.

OBJECTIVES: To evaluate diagnostic imaging costs before and after DTS implementation in patients with suspected thoracic lesions on CXR. METHODS: Four hundred sixty-five patients (263 male, 202 female; age, 72.47 ± 11.33 years) with suspected thoracic lesion(s) after CXR underwent DTS. Each patient underwent CT when a pulmonary non-calcified lesion was identified by DTS while CT was not performed when a benign pulmonary or extrapulmonary lesion or pseudolesion was identified. The average per-patient imaging cost was calculated by normalising the costs before and after DTS implementation. RESULTS: In 229/465 patients who underwent DTS after suspicious CXR, DTS showed 193 pulmonary lesions and 36 pleural lesions, while in the remaining 236/465 patients, lesions were ruled out as pseudolesions of CXR. Chest CT examination was performed in 127/465 (27 %) patients while in the remaining 338/465 patients (73 %) CXR doubtful findings were resolved by DTS. The average per-patient costs of CXR, DTS and CT were 15.15, 41.55 and 113.66. DTS allowed an annual cost saving of 8,090.2 considering unenhanced CT and 19,298.12 considering contrast-enhanced CT. Considering a DTS reimbursement rate of 62.7 the break even point corresponds to 479 DTS examinations. CONCLUSION: Per-patient diagnostic imaging costs decreased after DTS implementation in patients with suspected thoracic lesions. MAIN MESSAGES: • Digital tomosynthesis improves the diagnostic accuracy and confidence in chest radiography • Digital tomosynthesis reduces the need for CT for a suspected pulmonary lesion • Digital tomosynthesis requires a dose level equivalent to that of around two chest radiographies • Digital tomosynthesis produces a significant per-patient saving in diagnostic imaging costs.

Assessment of tissue perfusion by contrast-enhanced ultrasound.

Contrast-enhanced ultrasound (CEUS) with microbubble contrast agents is a new imaging technique for quantifying tissue perfusion. CEUS presents several advantages over other imaging techniques in assessing tissue perfusion, including the use of microbubbles as blood-pool agents, portability, availability and absence of exposure to radiation or nuclear tracers. Dedicated software packages are necessary to quantify the echo-signal intensity and allow the calculation of the degree of tissue contrast enhancement based on the accurate distinction between microbubble backscatter signals and native tissue background. The measurement of organ transit time after microbubble injection and the analysis of tissue reperfusion kinetics represent the two fundamental methods for the assessment of tissue perfusion by CEUS. Transit time measurement has been shown to be feasible and has started to become accepted as a clinical tool, especially in the liver. The loudness of audio signals from spectral Doppler analysis is used to generate time-intensity curves to follow the wash-in and wash-out of the microbubble bolus. Tissue perfusion may be quantified also by analysing the replenishment kinetics of the volume of microbubbles after their destruction in the imaged slice. This allows to obtain semiquantitative parameters related to local tissue perfusion, especially in the heart, brain, and kidneys.

Assessment of a new mathematical model for the computation of numerical parameters related to renal cortical blood flow and fractional blood volume by contrast-enhanced ultrasound.

We analyzed the value of a new mathematical model for the quantification of renal cortical blood flow and fractional blood volume by contrast-enhanced ultrasound after the injection of sulfur hexafluoride-filled microbubbles. A vessel-mimicking phantom experiment was preliminarily performed which showed that the effect of microbubble diffusion is negligible compared with the effect of liquid drag. Twelve healthy volunteers (7 male, 5 female; 27 to 48 years [n = 6; group 1], and 61 to 80 years [n = 6; group 2], respectively), with normal renal and cardiac function and not undergoing any pharmacologic treatment, were examined. In each volunteer, both kidneys were scanned after intravenous injection of sulfur hexafluoride-filled microbubbles at a slow rate (4.8 mL at a flow of 4.0 mL/min), and the refill kinetics of the renal cortex after microbubble destruction was evaluated by echo-signal intensity quantification. The progressive replenishment of the renal vessels was approximated both by standard negative exponential function and by the piecewise linear function resulting from our mathematical model. A better dataset approximation was provided by piecewise linear versus standard negative exponential function (overall mean square error: 0.44 vs. 0.51; p < 0.05, Wilcoxon test). The piecewise linear function provided a curve composed of four linear tracts (n = 3 volunteers; 2 from group 1 and 1 from group 2), three linear tracts (n = 6 volunteers; 3 from group 1 and 3 from group 2) or two linear tracts (n = 3 volunteers; 1 from group 1 and 2 from group 2). The piecewise linear function versus standard negative exponential function improved data approximation for the computation of numerical values related to renal cortical blood flow velocity and fractional blood volume.