Stress Perfusion Cardiac Magnetic Resonance vs SPECT Imaging for Detection of Coronary Artery Disease.

BACKGROUND: GadaCAD2 was 1 of 2 international, multicenter, prospective, Phase 3 clinical trials that led to U.S. Food and Drug Administration approval of gadobutrol to assess myocardial perfusion and late gadolinium enhancement (LGE) in adults with known or suspected coronary artery disease (CAD). OBJECTIVES: A prespecified secondary objective was to determine if stress perfusion cardiovascular magnetic resonance (CMR) was noninferior to single-photon emission computed tomography (SPECT) for detecting significant CAD and for excluding significant CAD. METHODS: Participants with known or suspected CAD underwent a research rest and stress perfusion CMR that was compared with a gated SPECT performed using standard clinical protocols. For CMR, adenosine or regadenoson served as vasodilators. The total dose of gadobutrol was 0.1 mmol/kg body weight. The standard of reference was a 70% stenosis defined by quantitative coronary angiography (QCA). A negative coronary computed tomography angiography could exclude CAD. Analysis was per patient. CMR, SPECT, and QCA were evaluated by independent central core lab readers blinded to clinical information. RESULTS: Participants were predominantly male (61.4% male; mean age 58.9 ± 10.2 years) and were recruited from the United States (75.0%), Australia (14.7%), Singapore (5.7%), and Canada (4.6%). The prevalence of significant CAD was 24.5% (n = 72 of 294). Stress perfusion CMR was statistically superior to gated SPECT for specificity (P = 0.002), area under the receiver operating characteristic curve (P < 0.001), accuracy (P = 0.003), positive predictive value (P < 0.001), and negative predictive value (P = 0.041). The sensitivity of CMR for a 70% QCA stenosis was noninferior and nonsuperior to gated SPECT. CONCLUSIONS: Vasodilator stress perfusion CMR, as performed with gadobutrol 0.1 mmol/kg body weight, had superior diagnostic accuracy for diagnosis and exclusion of significant CAD vs gated SPECT.

Gadobutrol-Enhanced Cardiac Magnetic Resonance Imaging for Detection of Coronary Artery Disease.

BACKGROUND: Gadolinium-based contrast agents were not approved in the United States for detecting coronary artery disease (CAD) prior to the current studies. OBJECTIVES: The purpose of this study was to determine the sensitivity and specificity of gadobutrol for detection of CAD by assessing myocardial perfusion and late gadolinium enhancement (LGE) imaging. METHODS: Two international, single-vendor, phase 3 clinical trials of near identical design, "GadaCAD1" and "GadaCAD2," were performed. Cardiovascular magnetic resonance (CMR) included gadobutrol-enhanced first-pass vasodilator stress and rest perfusion followed by LGE imaging. CAD was defined by quantitative coronary angiography (QCA) but computed tomography coronary angiography could exclude significant CAD. RESULTS: Because the design and results for GadaCAD1 (n = 376) and GadaCAD2 (n = 388) were very similar, results were summarized as a fixed-effect meta-analysis (n = 764). The prevalence of CAD was 27.8% defined by a ≥70% QCA stenosis. For detection of a ≥70% QCA stenosis, the sensitivity of CMR was 78.9%, specificity was 86.8%, and area under the curve was 0.871. The sensitivity and specificity for multivessel CAD was 87.4% and 73.0%. For detection of a 50% QCA stenosis, sensitivity was 64.6% and specificity was 86.6%. The optimal threshold for detecting CAD was a ≥67% QCA stenosis in GadaCAD1 and ≥63% QCA stenosis in GadaCAD2. CONCLUSIONS: Vasodilator stress and rest myocardial perfusion CMR and LGE imaging had high diagnostic accuracy for CAD in 2 phase 3 clinical trials. These findings supported the U.S. Food and Drug Administration approval of gadobutrol-enhanced CMR (0.1 mmol/kg) to assess myocardial perfusion and LGE in adult patients with known or suspected CAD.

Pharmacokinetics and Safety of Macrocyclic Gadobutrol in Children Aged Younger Than 2 Years Including Term Newborns in Comparison to Older Populations.

OBJECTIVES: This clinical study evaluated the pharmacokinetics (PK) and safety data of macrocyclic extracellular contrast agent gadobutrol in pediatric subjects aged younger than 2 years. MATERIALS AND METHODS: Pediatric subjects (term newborns to those aged younger than 2 years) with normal renal function undergoing magnetic resonance imaging with gadobutrol (0.1 mmol/kg body weight [BW]) were prospectively enrolled in this open-label, multicenter clinical trial to evaluate PK as a primary end point. Plasma PK was analyzed using a population-based PK approach. Safety and qualitative efficacy (evaluation of images) were secondary end points. Safety and tolerability were assessed throughout study participation (approximately 7 days). Imaging efficacy variables were assessed by investigators. RESULTS: Forty-four subjects were evaluated for safety and efficacy; 43 subjects were eligible for PK evaluation including 9 term newborns and infants aged younger than 2 months. Gadobutrol PK in pediatric subjects aged younger than 2 years were adequately described by a linear 2-compartmental model with elimination from the central compartment. Total median systemic exposure (area under the curve) of gadobutrol was estimated at 776 µmol · h/L (range, 544-1470 µmol · h/L). Simulated median concentration at 20 minutes after injection of gadobutrol (C20) was 339 µmol/L (range, 230-456 µmol/L). Safety and tolerability profile were similar to older populations. In 1 subject (2.3%), vomiting was reported as a mild adverse event related to gadobutrol, and there were no reported serious adverse events. The evaluation of gadobutrol-enhanced images provided improved diagnosis, increased confidence in diagnosis, and contributed to subject clinical management. CONCLUSIONS: The PK profile of gadobutrol in children aged younger than 2 years including newborns is similar to that in older children and adults. At the dose of 0.1 mmol/kg BW, gadobutrol had a favorable safety profile and was well tolerated with similar profile across the age range 0 to younger than 2 years and compared with older children and adults. Extrapolation of efficacy data from adults to the younger pediatric population, including term newborns, is justified. The recommended standard dose of gadobutrol (0.1 mmol/kg BW), as used in the population aged 2 years and older, is also appropriate in children aged younger than 2 years.

Toward a definition of MEG spike: parametric description of spikes recorded simultaneously by MEG and depth electrodes.

There is not yet a formal definition of magnetoencephalography (MEG) spike. This study provides a parametric description and definition of clear-cut MEG spikes recorded simultaneously by MEG and depth electrodes (iEEG). A total number of 367 simultaneous MEG/iEEG spikes were selected for analysis. Distribution of morphologic spike parameters and detailed quantitative analysis of the basic morphologic characteristics of MEG spikes is provided.

Simultaneous magnetoencephalography and intracranial EEG registration: technical and clinical aspects.

The purpose of this study was to describe the methodology necessary for simultaneous recording of intracranial EEG (ICEEG) and magnetoencephalography (MEG) and to assess the sensitivity of whole-head MEG versus depth electrode EEG in the detection and localization of epileptic spikes. Interictal MEG and depth electrode activities from the temporal mesial and occipital lobes were simultaneously recorded from four candidates for epilepsy surgery. Implanted depth electrodes identified neocortical and mesial structures of ictal onset. Interictal spikes detected by these same depth electrodes were compared with simultaneous MEG events. MEG detections of ICEEG spikes, ICEEG versus MEG spike amplitudes, number of ICEEG contacts involved in the spike, and anatomic locations of MEG equivalent current dipoles were analyzed. MEG detected and localized 95% of the neocortical spikes, but only 25% to 60% of spikes from mesial structures. Mesial temporal spikes resulted in lower MEG spike amplitudes, when compared with neocortical spikes. Equivalent current dipoles of MEG spikes localized to the ictal onset zones in all four patients. MEG can detect and localize interictal epileptiform spikes that are recorded from depth electrodes in both neocortical and mesial structures, despite the lesser amplitude of spikes of mesial origin.

Magnetoencephalography for research of auditory cortex.

CONCLUSION: The results could indicate that, during phylogeny and human ontogeny, the central nervous system has enhanced the speech activity from any other activity even though other frequencies could be relevant for survival. OBJECTIVE: People of all ages can experience alterations of auditory perception that progressively increase with aging. The whole approach to these alterations needs not only peripheral (cochlear) or brainstem studies but also an analysis of the auditory cortex. In fact, auditory evoked fields (AEF) may contribute to the understanding of the neural correlate of sound awareness. SUBJECTS AND METHODS: The M100 response after pure tone stimulation (five frequencies ranging from 500 to 8000 Hz) was analyzed in a group of nine adult subjects with normal hearing, older than 25 years of age and under 40 years old. Average M100 field intensity was calculated for all magnetoencephalography (MEG) channels in a 60 ms window around the M100 waveform. RESULTS: The results indicate a more intense cortical response to main speech frequencies (0.5 to 2 kHz) as compared with other frequencies not involved in human conversation.

Time modulated prefrontal and parietal activity during the maintenance of integrated information as revealed by magnetoencephalography.

Using magnetoencephalography, we investigated the spatiotemporal patterns of brain magnetic activity responsible for maintaining verbal and spatial information in either an integrated or an unintegrated fashion. Considering time dimension, we noted a greater activation of a fronto-parietal network in early latencies during the maintenance of integrated information, and a different pattern during the maintenance of unintegrated material, showing a greater activation in a fronto-posterior network in late latencies. The greater activation found in certain areas which are traditionally reported as being engaged in spatial working memory (i.e. superior frontal gyri, dorsolateral prefrontal cortex, superior and inferior parietal lobes) when subjects maintained integrated information could be explained by a greater weight of the spatial dimension. It is as if words somehow acquired a spatial attribute, thus exerting a greater load in a neural network specialized in spatial working memory. Alternatively, and not mutually exclusive, we also propose that during the maintenance of integrated information the allocation of cognitive resources is less interfering than during the maintenance of unintegrated information, making it easier.

Crisis del lóbulo temporal registrada mediante magnetoencefalografía: caso clínico / Temporal lobe seizure recorded by magnetoencephalography: case report

La localización del inicio de las crisis es un factor importante para la evaluación prequirúrgica de la epilepsia. En este trabajo se describe la localización del inicio de una crisis registrada mediante magnetoencefalografía (MEG) en un niño de 12 años que presenta crisis parciales complejas farmacorresistentes. La RM muestra una lesión de 20mm de diámetro en el hipocampo izquierdo. EEG de superficie con ondas theta temporales izquierdas. Registro MEG interictal con punta-onda aislada posterior e inferior a la lesión de la RM. Registro MEG ictal con punta-onda (2 Hz). La localización de los dipolos indica el inicio de la crisis en la circunvolución temporal inferior en la misma localización que la actividad interictal MEG. Esta actividad ictal se propaga bilateralmente a áreas frontales. El registro corticográfico intraquirúrgico confirma los resultados de la localización interictal mediante MEG.

[Temporal lobe seizure recorded by magnetoencephalography: case report]. / Crisis del lóbulo temporal registrada mediante magnetoencefalografía: caso clínico.

Ictal onset localization is a important factor in presurgical evaluation of epilepsy. This paper describes the localization of a seizure onset recorded by magnetoencephalography (MEG) from a 12-year-old male patient who suffered from complex partial drug-resistant seizures. MRI revealed a 20mm diameter lesion located in left hippocampus. Scalp EEG showed left temporal theta waves. Interictal MEG registrations detected isolated spike-wave activity posterior and inferior to the MRI lesion. Ictal MEG showed continuous spike-wave activity (2 Hz). Dipole localization sited seizure onset in the inferior left temporal gyrus, the same localization of the interictal MEG activity. This ictal activity spreads bilaterally to frontal areas. Intrasurgical electrocorticography recording confirmed interictal MEG results.