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.

CT features of pulmonary arterial hypertension and its major subtypes: a systematic CT evaluation of 292 patients from the ASPIRE Registry.

We evaluated the prevalence and prognostic value of CT-pulmonary angiographic (CTPA) measures in 292 treatment naive patients with pulmonary arterial hypertension (PAH). Pulmonary artery calcification (13%) and thrombus (10%) were exclusively seen in PAH-congenital heart disease. Oesophageal dilation (46%) was most frequent in PAH-systemic sclerosis. Ground glass opacification (GGO) (41%), pericardial effusion (38%), lymphadenopathy (19%) and pleural effusion (11%) were common. On multivariate analysis, inferior vena caval area, the presence of pleural effusion and septal lines predicted outcome. In PAH, CTPA provides diagnostic and prognostic information. In addition, the presence of GGO on a CT performed for unexplained breathlessness should alert the physician to the possibility of PAH.

Lung ventilation volumetry with same-breath acquisition of hyperpolarized gas and proton MRI.

The purpose of this work was to assess the reproducibility of percentage of ventilated lung volume (PV) measured from hyperpolarized (HP) (3)He and (1)H anatomical images acquired in the same breath-hold when compared with PV measured from (3)He and (1)H images from separate breath-holds. Volumetric (3)He ventilation and (1)H anatomical images of the same resolution were acquired during the same breath-hold. To assess reproducibility, this procedure was performed twice with a short gap between acquisitions. In addition, (1)H images were also acquired in a separate breath for comparison. PV ((3)He ventilated volume divided by (1)H total lung volume) was calculated using the single-breath-hold images (PV(single)) and the separate-breath-hold images (PV(separate)). Short-term reproducibility of PV measurement was assessed for both single- and separate-breath acquisitions. Dice similarity coefficients (DSCs) were calculated to quantify spatial overlap between (3)He and (1)H segmentations for the single- and separate-breath-hold acquisitions. The efficacy of using the separate-breath method combined with image registration was also assessed. The mean magnitude difference between the two sets of PV values (±standard deviation) was 1.49 ± 1.32% for PV(single) and 4.19 ± 4.10% for PV(separate), with a significant difference (p < 0.01). The mean magnitude difference between the two PV values for the registered separate-breath technique (PV(sep-registered)) was 2.27 ± 2.23%. Bland-Altman analysis showed that PV measured with single-breath acquisitions was more repeatable than PV measured with separate-breath acquisitions, regardless of image registration. DSC values were significantly greater (p < 0.01) for single-breath acquisition than for separate-breath acquisition. Acquisition of HP gas ventilation and (1)H anatomical images in a single breath-hold provides a more reproducible means of percentage lung ventilation volume measurement than the previously used separate-breath-hold scan approach, and reduces errors.

Incorporation of prior knowledge in compressed sensing for faster acquisition of hyperpolarized gas images.

Adding prior knowledge to compressed sensing reconstruction can improve image reconstruction. In this work, two approaches are investigated to improve reconstruction of two-dimensional hyperpolarized (3)He lung ventilation images using prior knowledge. When compared against a standard compressed sensing reconstruction, the proposed methods allowed acquisition of images with higher under-sampling factors and reduction of the blurring effects that increase with higher reduction factors when fixed flip angles are used. These methods incorporate the prior knowledge of polarization decay of hyperpolarized (3)He and the mutual anatomical information from a registered (1)H image acquired in the same breath. Three times accelerated two-dimensional images reconstructed with compressed sensing and prior knowledge gave lower root-mean square error, than images reconstructed without introduction of any prior information. When introducing the polarization decay as prior knowledge, a significant improvement was achieved in the lung region, the root mean square value decreased by 45% and from the whole image by 36%. When introducing the mutual anatomical information as prior knowledge, the root mean square decreased by 21% over the lung region and by 15% over the whole image.

Group sparse reconstruction using intensity-based clustering.

Compressed sensing has been of great interest to speed up the acquisition of MR images. The k-t group sparse (k-t GS) method has recently been introduced for dynamic MR images to exploit not just the sparsity, as in compressed sensing, but also the spatial group structure in the sparse representation. k-t GS achieves higher acceleration factors compared to the conventional compressed sensing method. However, it assumes a spatial structure in the sparse representation and it requires a time consuming hard-thresholding reconstruction scheme. In this work, we propose to modify k-t GS by incorporating prior information about the sorted intensity of the signal in the sparse representation, for a more general and robust group assignment. This approach is referred to as group sparse reconstruction using intensity-based clustering. The feasibility of the proposed method is demonstrated for static 3D hyperpolarized lung images and applications with both dynamic and intensity changes, such as 2D cine and perfusion cardiac MRI, with retrospective undersampling. For all reported acceleration factors the proposed method outperforms the original compressed sensing method. Improved reconstruction over k-t GS method is demonstrated when k-t GS assumptions are not satisfied. The proposed method was also applied to cardiac cine images with a prospective sevenfold acceleration, outperforming the standard compressed sensing reconstruction.

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 influence of field strength on the apparent diffusion coefficient of 3He gas in human lungs.

The (3)He MR diffusion signal is sensitive to lung microstructure, but it is also affected by the presence of background field inhomogeneities induced by the magnetic susceptibility difference at the air-tissue interface. These susceptibility-induced gradients, which are dependent on field strength, have been assumed negligible in theoretical models used to extract airway morphometric information from (3)He MR diffusion data at field strengths up to 4.7 T. In this work, the effect of susceptibility gradients on (3)He apparent diffusion coefficient is demonstrated with experiments in healthy volunteers at two B(0) field strengths: 1.5 and 3 T. Apparent diffusion coefficient values obtained at 3 T were systematically larger than at 1.5 T, demonstrating that susceptibility effects are statistically significant even at clinical field strengths (B(0) ≤ 3 T) and introduce biases in the estimates of airway dimensions (e.g., mean linear intercept up to 17% larger at 3 T than 1.5 T). Susceptibility effects should be taken into account in the development of theoretical models of lung (3)He MR diffusion and considered when interpreting (3)He apparent diffusion coefficients obtained at different B(0).

Acquisition of ³He ventilation images, ADC, T2* and B1 maps in a single scan with compressed sensing.

In imaging of human lungs with hyperpolarised noble gases, measurements of apparent diffusion coefficient (ADC) and relaxation time provide valuable information for the assessment of lung microstructure. In this work, a sequence was developed for interleaved acquisition of ventilation images, ADC, T(2)* and flip angle maps in a single scan from the human lungs with a single dose of inhaled (3)He at 3 T. Spatially registered ventilation images with parametric maps were obtained. The total acquisition time was reduced by random undersampling of the k-space and reconstruction using compressed sensing (CS). The gain in speed was used for an increase in spatial resolution. Mean ADC values from the fully sampled and undersampled CS data exhibit no statistically significant difference in a given subject. The mean T(2)* values, however, were found to differ significantly, which is attributed to the combined effect of low signal-to-noise ratio (SNR) of the fully sampled data and the smoothing effect inherent in CS reconstruction.

Hyperpolarised 3He MRI versus HRCT in COPD and normal volunteers: PHIL trial.

The aim of the present study was to apply hyperpolarised (HP) (3)He magnetic resonance imaging (MRI) to identify patients with chronic obstructive pulmonary disease (COPD) and alpha(1)-antitrypsin deficiency (alpha(1)-ATD) from healthy volunteers and compare HP (3)He MRI findings with high-resolution computed tomography (HRCT) in a multicentre study. Quantitative measurements of HP (3)He MRI (apparent diffusion coefficient (ADC)) and HRCT (mean lung density (MLD)) were correlated with pulmonary function tests. A prospective three centre study enrolled 122 subjects with COPD (either acquired or genetic) and age-matched never-smokers. All diagnostic studies were completed in 94 subjects (52 with COPD; 13 with alpha(1)-ATD; 29 healthy subjects; 63 males; and 31 females; median age 62 yrs). The consensus assessment of radiologists, blinded for other test results, estimated nonventilated lung volume (HP (3)He MRI) and percentage diseased lung (HRCT). Quantitative evaluation of all data for each centre consisted of ADC (HP (3)He MRI) and MLD measurements (HRCT), and correlation with forced expiratory volume in 1 s (FEV(1))/forced vital capacity (FVC) indicating airway obstruction, and the diffusing capacity of the lung for carbon monoxide (D(L,CO)) indicating alveolar destruction. Using lung function tests as a reference, regional analysis of HP (3)He MRI and HRCT correctly categorised normal volunteers in 100% and 97%, COPD in 42% and 69% and alpha(1)-ATD in 69% and 85% of cases, respectively. Direct comparison of HP (3)He MRI and CT revealed 23% of subjects with moderate/severe structural abnormalities had only mild ventilation defects. In comparison with lung function tests, ADC was more effective in separating COPD patients from healthy subjects than MLD (p<0.001 versus 0.038). ADC measurements showed better correlation with D(L,CO) than MLD (r = 0.59 versus 0.29). Hyperpolarised (3)He MRI correctly categorised patients with COPD and normal volunteers. It offers additional functional information, without the use of ionising radiation whereas HRCT gives better morphological information. We showed the feasibility of a multicentre study using different magnetic resonance systems.

Raphe inhibition of sympathetic preganglionic neurons.

Anatomical and electrophysiological studies suggest that the medullary raphe gives rise to a monosynaptic, inhibitory projection on sympathetic preganglionic neurons. Physiological and behavioral data indicate that this sympathoinhibitory pathway participates in the central control of cardiovascular function.

Some dissociating factors in the analysis of structural and functional progressive damage in open-angle glaucoma.

AIM: To identify the presence, and origin, of any "dissociating factors" inherent to the techniques for evaluating progression that mask the relationship between structural and functional progression in open-angle glaucoma (OAG). METHODS: 23 patients (14 with OAG and 9 with ocular hypertension (OHT)) who had received serial Heidelberg Retina Tomograph (HRT II) and Humphrey Field Analyser (HFA) examinations for >or=5 years (mean 78.4 months (SD 9.5), range 60-101 months) were identified. Evidence of progressive disease was retrospectively evaluated in one eye of each patient using the Topographic Change Analysis (TCA) and Glaucoma Progression Analysis (GPA) for the HRT II and HFA, respectively. RESULTS: Six patients were stable by both techniques; four exhibited both structural and functional progression; seven exhibited structural progression, only, and six showed functional progression, only. Three types of dissociating factors were identified. TCA failed to identify progressive structural damage in the presence of advanced optic nerve head damage. GPA failed to identify progressive functional damage at stimulus locations, with sensitivities exhibiting test-retest variability beyond the maximum stimulus luminance of the perimeter, and where a perimetric learning effect was apparent. CONCLUSION: The three dissociating factors accounted for nine of the 13 patients who exhibited a lack of concordance between structural and functional progressive damage.

Combined simulated annealing and Shinnar-Le Roux pulse design of slice-multiplexed RF pulses for multi-slice imaging.

Slice-multiplexed RF pulses have recently been introduced for simultaneous multi-slice imaging. Their novel aspect is that each slice is given a different linear phase profile, and hence a different slice-rephasing requirement, by the pulse. During readout, extra slice gradients are applied such that when one slice is rephased, the others are dephased to prevent aliasing. In this paper, an improved method of designing slice-multiplexed RF pulses is presented: component pulses which are optimized with simulated annealing for a specific rephasing are combined using Shinnar-Le Roux methods. In this way, non-linearities at higher flip angles are taken into account and more slices can be excited. Bloch simulations show the phase and amplitude profile of component pulses are faithfully preserved in the multiplexed pulse. Three- and four-slice multiplex pulses are demonstrated in gradient- and spin-echo in-vivo imaging.

Functional Image-guided Radiotherapy Planning for Normal Lung Avoidance.

For patients with lung cancer undergoing curative intent radiotherapy, functional lung imaging can be incorporated into treatment planning to modify the dose distribution within non-target volume lung by differentiation of lung regions that are functionally defective or viable. This concept of functional image-guided lung avoidance treatment planning has been investigated with several imaging modalities, primarily single photon emission computed tomography (SPECT), but also hyperpolarised gas magnetic resonance (MR) imaging, positron emission tomography (PET) and computed tomography (CT)-based measures of lung biomechanics. Here, we review the application of each of these modalities, review practical issues of lung avoidance implementation, including image registration and the role of both ventilation and perfusion imaging, and provide guidelines for reporting of future lung avoidance planning studies.

Discrimination of glaucomatous optic neuropathy by digital stereoscopic analysis.

PURPOSE: To evaluate the diagnostic power of a novel digital stereoscopic imaging system in the diagnosis of glaucomatous optic neuropathy. DESIGN: Prospective cross-sectional analysis of the diagnostic accuracy of digital stereoscopic optic disc analysis in the diagnosis of glaucomatous optic neuropathy exhibiting mild to moderate field loss. PARTICIPANTS: Fifty-two patients with open-angle glaucoma and 54 normal individuals were recruited. The presence of a reproducible visual field loss characteristic of glaucoma was used as the reference standard for the presence of glaucoma independent of the optic nerve head appearance. Patients were excluded if the optic disc, fundus, or visual field indicated other disease. One eye from each patient and individual was included in the study, the eye with the least field loss and a randomly designated normal eye, respectively. METHODS: Simultaneous stereoscopic optic disc photography was performed on each specified eye. Three experienced observers viewed the resultant stereoscopic image of each nerve head using a Z screen, recorded a subjective clinical diagnosis, and undertook digital stereoscopic planimetry. Separate linear regression analysis was performed, post hoc, from the planimetric results for each observer of the logarithm of neuroretinal rim (NRR) against optic disc area derived from each normal eye. Eyes with NRR areas below the 95th prediction interval of the normal cohort were then classified as glaucomatous. MAIN OUTCOME MEASURES: Sensitivity and specificity for the detection of glaucomatous optic neuropathy. RESULTS: With subjective stereoscopic analysis, sensitivity for glaucoma detection among the 3 observers was 80.8%, 76.9%, and 90.4%, with respective specificities of 94.4%, 79.6%, and 79.6%. Regression analysis of the NRR in 30 degrees segments gave sensitivities between 69.2% and 80.8% and specificities between 83.3% and 90.7%. A combination of the subjective and quantitative analysis did not significantly improve discrimination. CONCLUSIONS: The subjective analysis of digital stereoscopic images provides a useful method for the discrimination of normal and glaucomatous optic nerves. Planimetric analysis does not significantly improve the diagnostic precision of this technique.

N-acetylaspartate distribution in proton spectroscopic images of ischemic stroke: relationship to infarct appearance on T2-weighted magnetic resonance imaging.

BACKGROUND AND PURPOSE: It is generally considered that tissue that appears abnormal on T2 MRI is already infarcted and that any penumbra lies outside the T2-visible lesion. We investigated the distribution of infarcted tissue using proton spectroscopic MRI. METHODS: In patients with symptoms of acute hemispheric ischemic stroke, imaged within a maximum of 3 days of stroke, we explored the distribution of N:-acetylaspartate (NAA), a marker of intact neurons, within and around the abnormal (hyperintense) areas on T2-weighted MR images, using proton spectroscopic MRI. RESULTS: In 11 patients, imaged 24 to 72 hours after stroke onset, there was little evidence of damaged neurons (reduced NAA) beyond the margins of hyperintensity on the T2 image. However, within the abnormal T2 area, there were statistically significant differences in the amount of NAA (ie, the proportion of intact neurons) between areas that were obviously abnormal on T2 (very hyperintense) and those that were only slightly abnormal (slightly hyperintense). CONCLUSIONS: The extent and degree of hyperintensity of the T2-visible lesion directly reflect the amount of neuronal damage; lack of a T2-visible lesion would suggest predominantly intact neurons at the time of imaging. We hypothesize that once tissue damage has reached a critical (probably irreversible) level, the T2 image quickly becomes abnormal without any significant time lag between the pathological staging of the infarct and its visualization on T2. Further testing in a larger study with information on blood flow levels would be required to confirm this.

Descending projections of the songbird nucleus robustus archistriatalis.

The descending, efferent projections of nucleus robustus archistriatalis were investigated in male zebra finches and greenfinches with injections of either biotinylated dextran amine or cholera toxin B-chain conjugated to horseradish peroxidase. The results show that in addition to the well-known projections to the tracheosyringeal motor nucleus and the dorsomedial nucleus of the intercollicular complex, there are other projections of comparable density to the ipsilateral nucleus ambiguus and nucleus retroambigualis. Within nucleus ambiguus, robustus axons terminate in close proximity to laryngeal motoneurons which were retrogradely labelled in the same bird by injections of cholera B-chain into the laryngeal muscles; and within nucleus retroambigualis robustus axons terminate in relation to bulbospinal neurons previously shown to project to regions of spinal cord containing motoneurons innervating abdominal expiratory muscles (J.M. Wild, Brain Res. 606:119-124, 1993). These projections of nucleus robustus thus seem well placed to coordinate syringeal, laryngeal, and expiratory muscle activity during vocalization. Other relatively sparse, but distinct, projections of nucleus robustus were found to nucleus dorsolateralis anterior thalami, pars medialis, to a narrow region between the superior olivary nucleus and the spinal lemniscus, and to the rostral ventrolateral medulla. Neurons in these last two locations were retrogradely labelled bilaterally following injections of cholera B-chain into nucleus retroambigualis of one side. Together with sparse contralateral projections of nucleus robustus to all brainstem targets receiving ipsilateral projections, potential pathways are thus identified by which the respiratory-vocal activity controlled by one side of the lower medulla can be influenced by the nucleus robustus of either side, thereby possibly bringing about bilateral coordination of respiratory-vocal output.

Convergence of somatosensory and auditory projections in the avian torus semicircularis, including the central auditory nucleus.

Projections of dorsal column, spinal, and cochlear nuclei upon the central nucleus of the torus semicircularis (otherwise known as nucleus mesencephalicus lateralis, pars dorsalis, or MLd) and upon other toral nuclei were investigated in pigeon by anterograde and retrograde tracing and electrophysiological methods. The anatomical results showed that caudal regions of the dorsal column nuclei and medial lamina V of the upper four cervical spinal segments have extensive projections upon the contralateral central auditory nucleus and upon other nuclei of the torus, in particular the core portion of the preisthmic superficial area of Puelles et al. (L. Puelles, C. Rrobles, M. Martiez-de-la-Torre, and S. Martinez, 1994, J. Comp. Neurol. 340:98-125). The projections of nucleus angularis were found to terminate throughout most of the contralateral central nucleus except the dorsomedial portion at rostral levels, where the majority of the projections of nucleus laminaris were concentrated. Nucleus angularis (and to a lesser extent nucleus laminaris) was also found to have substantial projections to certain noncentral toral nuclei, in particular to the caudomedial shell nucleus of Puelles et al. (1994). As shown positively with both Nissl and cytochrome oxidase staining and negatively with substance P labeling, this nucleus is a medial extension of more caudal regions of the central nucleus, and it is suggested that it should be included as part of the auditory midbrain. The electrophysiological results confirmed the anatomical findings by showing that evoked potentials and multiunit activity can be recorded throughout the central and noncentral toral nuclei by using electrical stimulation of the radial nerve and auditory click stimuli. The core portion of the preisthmic superficial area, however, can be regarded as a distinct somatosensory nucleus of the midbrain. It is concluded that there is substantial convergence of somatosensory and auditory inputs within both central auditory and noncentral nuclei of the torus semicircularis in pigeon.

Direct and indirect "cortico"-rubral and rubro-cerebellar cortical projections in the pigeon.

In birds the red nucleus is the most rostral cell group in the brain having projections to all levels of the spinal cord (Cabot et al., Prog. Brain Res., 57:79-108, 1982), but its sources of afferents are incompletely known. In order to determine these, a series retrograde and anterograde tracing experiments was carried out, largely with cholera toxin B-chain conjugated to horseradish peroxidase. The results show that a sparse and diffuse projection to the red nucleus arises from deep regions of the hyperstriatum accessorium (HA) of the anterior Wulst, and that a much more dense projection arises from the caudal part of the nucleus principalis precommissuralis and the medial part of the medial spiriform nucleus (SpMm). These last two sources were themselves shown to receive a substantial projection from HA of the anterior Wulst. The red nucleus was also shown to project upon the cerebellar cortex of lobule VI, and SpM upon the cerebellar cortex of lobules VI through IX (Karten and Finger, Brain Res., 102:335-338, 1976; Clarke, J. Comp. Neurol., 174:535-552, 1977). Double retrograde labelling experiments with fluorescein and rhodamine labelled latex microspheres injected into the cerebellar cortex and spinal cord showed that the rubrocerebellar cortical neurons are a different population from, although intermixed with, the rubrospinal neurons.