Non-invasive methods for estimating mPAP in COPD using cardiovascular magnetic resonance imaging.

PURPOSE: Pulmonary hypertension (PH) is associated with a poor outcome in chronic obstructive pulmonary disease (COPD) and is diagnosed invasively. We aimed to assess the diagnostic accuracy and prognostic value of non-invasive cardiovascular magnetic resonance (CMR) models. METHODS: Patients with COPD and suspected PH, who underwent CMR and right heart catheter (RHC) were identified. Three candidate models were assessed: 1, CMR-RV model, based on right ventricular (RV) mass and interventricular septal angle; 2, CMR PA/RV includes RV mass, septal angle and pulmonary artery (PA) measurements; 3, the Alpha index, based on RV ejection fraction and PA size. RESULTS: Of 102 COPD patients, 87 had PH. The CMR-PA/RV model had the strongest diagnostic accuracy (sensitivity 92%, specificity 80%, positive predictive value 96% and negative predictive value 63%, AUC 0.93, p<0.0001). Splitting RHC-mPAP, CMR-RV and CMR-PA/RV models by 35mmHg gave a significant difference in survival, with log-rank chi-squared 5.03, 5.47 and 7.10. RV mass and PA relative area change were the independent predictors of mortality at multivariate Cox regression (p=0.002 and 0.030). CONCLUSION: CMR provides diagnostic and prognostic information in PH-COPD. The CMR-PA/RV model is useful for diagnosis, the RV mass index and PA relative area change are useful to assess prognosis. KEY POINTS: • Pulmonary hypertension is a marker of poor outcome in COPD. • MRI can predict invasively measured mean pulmonary artery pressure. • Cardiac MRI allows for estimation of survival in COPD. • Cardiac MRI may be useful for follow up or future trials. • MRI is potentially useful to assess pulmonary hypertension in patients with COPD.

MRI model-based non-invasive differential diagnosis in pulmonary hypertension.

Pulmonary hypertension(PH) is a disorder characterised by increased mean pulmonary arterial pressure. Currently, the diagnosis of PH relies upon measurements taken during invasive right heart catheterisation (RHC). This paper describes a process to derive diagnostic parameters using only non-invasive methods based upon MRI imaging alone. Simultaneous measurements of main pulmonary artery (MPA) anatomy and flow are interpreted by 0D and 1D mathematical models, in order to infer the physiological status of the pulmonary circulation. Results are reported for 35 subjects, 27 of whom were patients clinically investigated for PH and eight of whom were healthy volunteers. The patients were divided into 3 sub-groups according to the severity of the disease state, one of which represented a negative diagnosis (NoPH), depending on the results of the clinical investigation, which included RHC and complementary MR imaging. Diagnostic indices are derived from two independent mathematical models, one based on the 1D wave equation and one based on an RCR Windkessel model. Using the first model it is shown that there is an increase in the ratio of the power in the reflected wave to that in the incident wave (Wpb/Wptotal) according to the classification of the disease state. Similarly, the second model shows an increase in the distal resistance with the disease status. The results of this pilot study demonstrate that there are statistically significant differences in the parameters derived from the proposed models depending on disease status, and thus suggest the potential for development of a non-invasive, image-based diagnostic test for pulmonary hypertension.

ASPIRE registry: assessing the Spectrum of Pulmonary hypertension Identified at a REferral centre.

Pulmonary hypertension (PH) is a heterogeneous condition. To date, no registry data exists reflecting the spectrum of disease across the five diagnostic groups encountered in a specialist referral centre. Data was retrieved for consecutive, treatment-naïve cases diagnosed between 2001 and 2010 using a catheter-based approach. 1,344 patients were enrolled, with a mean follow-up of 2.9 yrs. The 3-yr survival was 68% for pulmonary arterial hypertension (PAH), 73% for PH associated with left heart disease, 44% for PH associated with lung disease (PH-lung), 71% for chronic thromboembolic PH (CTEPH) and 59% for miscellaneous PH. Compared with PAH, survival was inferior in PH-lung and superior in CTEPH (p<0.05). Multivariate analysis demonstrated that diagnostic group independently predicted survival. Within PAH, Eisenmenger's survival was superior to idiopathic PAH, which was superior to PAH associated with systemic sclerosis (p<0.005). Within PH-lung, 3-yr survival in sleep disorders/alveolar hypoventilation (90%) was superior to PH-lung with chronic obstructive pulmonary disease (41%) and interstitial lung disease (16%) (p<0.05). In CTEPH, long-term survival was best in patients with surgically accessible disease undergoing pulmonary endarterectomy. In this large registry of consecutive, treatment-naïve patients identified at a specialist PH centre, outcomes and characteristics differed between and within PH groups. The current system of classification of PH has prognostic value even when adjusted for age and disease severity, emphasising the importance of systematic evaluation and precise classification.

The high incidence and bioethics of findings on magnetic resonance brain imaging of normal volunteers for neuroscience research.

BACKGROUND: We were finding volunteers for functional magnetic resonance imaging studies with abnormalities requiring referral surprisingly frequently. The bioethics surrounding the incidental findings are not straightforward and every imaging institution will encounter this situation in their normal volunteers. Yet the implications for the individuals involved may be profound. Should all participants have review of their imaging by an expert and who should be informed? METHODS: The normal volunteers that were imaged with magnetic resonance (MR) which were reviewed by a consultant neuroradiologist. All participants completed a volunteer consent form in addition to a standard departmental MR safety screening form. The volunteer screening form requires the general practitioner details to be completed and asks the participant to consider closely the possibility and implications of finding an unexpected but potentially serious abnormality before signing. RESULTS: 525 different individuals were scanned as normal volunteers, the mean age was 35-years and 330 were males. Of these 525, 46 had definite significant abnormalities (8.8%), mean age 50-years. CONCLUSION: We have found a high rate of incidental abnormalities amongst individuals participating in imaging studies at our institution. It is our current practice to inform the research study participant of the findings, counsel them and inform their primary care physician. We think that it is advisable for researchers utilising MR imaging of the brain to have access to trained neuroradiologists, a protocol in place to deal with this problem and take consent in a way that allows the participant to realise the possibility of an abnormal finding.

Stereotactic radiosurgery for brain arteriovenous malformations: quantitative MR assessment of nidal response at 1 year and angiographic factors predicting early obliteration.

INTRODUCTION: We investigated the role of magnetic resonance angiography (MRA) in the early follow-up of patients after stereotactic radiosurgery (STRS) for cerebral arteriovenous malformations (AVMs) and determined the influence of individual morphological factors of AVMs in early response to treatment. METHODS: A group of 40 patients (41 AVMs) consented to a dedicated 1.5-T MR protocol 12 months after receiving STRS for a brain AVM. In addition to standard spin echo sequences, 3-D contrast-enhanced sliding interleaved Ky MRA (CE-SLINKY) and dynamic time-resolved subtraction angiography (MR-DSA) were performed. Nidal volumes were calculated using CE-SLINKY data in patients with a persisting arteriovenous shunt. Planning angiographic data was investigated in all 40 patients. The following AVM factors were used in the statistical analysis to determine their role in nidus obliteration: (1) maximum linear dimension, (2) nidal volume, (3) AVM location (4) nidal morphology, (5) venous drainage, (6) "high-flow angiographic change", (7) prior embolization, and (8) dose reduction. RESULTS: Complete nidal obliteration was found in 9 patients, 26 showed greater than 50% nidal reduction and 6 had less than 50%. Two AVM factors, venous drainage and AVM location, were found to significantly correlate with rate of obliteration. CONCLUSION: We successfully demonstrated the use of MRA to quantitatively assess the response of AVMs to STRS. Two AVM factors, venous drainage and AVM location were found to correlate with rate of obliteration prior to the application of the Bonferroni correction, but if this more rigorous statistical test was applied then none of the factors was found to be significant.

Brain arteriovenous malformations: measurement of nidal volume using a combination of static and dynamic magnetic resonance angiography techniques.

Arteriovenous malformations of the brain are complex vascular lesions that are an important cause of death and long-term disability. Currently, catheter angiography (CA) is the reference standard procedure for the diagnosis and follow-up of treated arteriovenous malformations (AVMs). This is an invasive procedure with potential risks. Magnetic resonance angiography (MRA) is commonly used in neurovascular imaging as a non-invasive alternative. Various MRA techniques have been used in the diagnosis and follow-up of AVMs but these have suffered from lack of temporal or spatial resolution. In this 60-patient study we describe the combination of two techniques: dynamic magnetic resonance digital subtraction angiography with a high temporal resolution, and a non-dynamic contrast-enhanced time-of-flight sequence with a high spatial resolution technique, in the assessment of AVM. The results showed an excellent correlation between MRA and CA measurement of both maximum linear dimension and AVM nidus volume.

Analysis of the conserved acidic residues in the regulatory domain of PhoB.

The PhoB protein from Escherichia coli is a member of the two-component signal transduction pathway that controls an adaptive response to limiting phosphate. Activation involves its phosphorylation on a conserved aspartate. Site-directed mutations were introduced at conserved acidic residues. The E9D, D10E, D10N, E11A, E11D and E11Q mutants were each able to induce alkaline phosphatase under low phosphate growth conditions whereas the E9A, D10A, D53A, D53E and D53N could not. The E9Q mutant was constitutively active. Phosphorylation assays showed that only the E9D, E11A, E11Q and E11D mutants were phosphorylated by acetyl phosphate. Most mutants also displayed defects in magnesium binding.