Richard Frayne

Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration

Summary Cerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE).

Characterization of common carotid artery blood-flow waveforms in normal human subjects

Knowledge of human blood-flow waveforms is required for in vitro investigations and numerical modelling. Parameters of interest include: velocity and flow waveform shapes, inter- and intra-subject variability and frequency content. We characterized the blood-velocity waveforms in the left and right common carotid arteries (CCAs) of 17 normal volunteers (24 to 34 years), analysing 3560 cardiac cycles in total. Instantaneous peak-velocity (Vpeak) measurements were obtained using pulsed-Doppler ultrasound with simultaneous collection of ECG data. An archetypal Vpeak waveform was created using velocity and timing parameters at waveform feature points. We report the following timing (post-R-wave) and peak-velocity parameters: cardiac interbeat interval (T(RR)) = 0.917 s (intra-subject standard deviation = +/- 0.045 s); cycle-averaged peak-velocity (V(CYC)) = 38.8 cm s(-1) (+/-1.5 cm s(-1)); maximum systolic Vpeak = 108.2 cm s(-1) (+/-3.8 cm s(-1)) at 0.152 s (+/-0.008 s); dicrotic notch Vpeak = 19.4 cm s(-1) (+/-2.9 cm s(-1)) at 0.398 s (+/-0.007 s). Frequency components below 12 Hz constituted 95% of the amplitude spectrum. Flow waveforms were computed from Vpeak by analytical solution of Womersley flow conditions (derived mean flow = 6.0 ml s(-1)). We propose that realistic, pseudo-random flow waveform sequences can be generated for experimental studies by varying, from cycle to cycle, only T(RR) and V(CYC) of a single archetypal waveform.

Imaging of the brain in acute ischaemic stroke: comparison of computed tomography and magnetic resonance diffusion-weighted imaging.

Background and objectives: Controversy exists about the optimal imaging technique in acute stroke. It was hypothesised that CT is comparable with DWI, when both are read systematically using quantitative scoring. Methods: Ischaemic stroke patients who had CT within six hours and DWI within seven hours of onset were included. Five readers used a quantitative scoring system (ASPECTS) to read the baseline (b) and follow up CT and DWI. Use of MRI in acute stroke was also assessed in patients treated with tissue plasminogen activator (tPA) by prospectively recording reasons for exclusion. Patients were followed clinically at three months. Results: bDWI and bCT were available for 100 consecutive patients (admission median NIHSS = 9). The mean bDWI and bCT ASPECTS were positively related (p<0.001). The level of interrater agreement ranged from good to excellent across all modalities and time periods. Bland–Altman plots showed more variability between bCT and bDWI than at 24 hours. The difference between bCT and bDWI was ⩽2 ASPECTS points. Of bCT scans with ASPECTS 8–10, 81% had DWI ASPECTS 8–10. Patients with bCT ASPECTS of 8–10 were 1.9 times more likely to have a favourable outcome at 90 days than those with a score of 0–7 (95% CI 1.1 to 3.1, p = 0.002). The relative likelihood of favourable outcome with a bDWI ASPECTS 8–10 was 1.4 (95% CI 1.0 to 1.9, p = 0.10). Of patients receiving tPA 45% had contraindications to urgent MRI. Conclusion: The differences between CT and DWI in visualising early infarction are small when using ASPECTS. CT is faster and more accessible than MRI, and therefore is the better neuroimaging modality for the treatment of acute stroke.

Magnetic resonance imaging at 3.0 Tesla: challenges and advantages in clinical neurological imaging.

MR imaging at very high field (3.0 T) is a significant new clinical tool in the modern neuroradiological armamentarium. In this report, we summarize our 40-month experience in performing clinical neuroradiological examinations at 3.0 T and review the relevant technical issues. We report on these issues and, where appropriate, their solutions. Issues examined include: increased SNR, larger chemical shifts, additional problems associated with installation of these scanners, challenges in designing and obtaining appropriate clinical imaging coils, greater acoustic noise, increased power deposition, changes in relaxation rates and susceptibility effects, and issues surrounding the safety and compatibility of implanted devices. Some of the these technical factors are advantageous (eg, increased signal-to-noise ratio), some are detrimental (eg, installation, coil design and development, acoustic noise, power deposition, device compatibility, and safety), and a few have both benefits and disadvantages (eg, changes in relaxation, chemical shift, and susceptibility). Fortunately solutions have been developed or are currently under development, by us and by others, for nearly all of these challenges. A short series of 1.5 T and 3.0 T patient images are also presented to illustrate the potential diagnostic benefits of scanning at higher field strengths. In summary, by paying appropriate attention to the discussed technical issues, high-quality neuro-imaging of patients is possible at 3.0 T.

Susceptibility-Weighted Imaging is More Reliable Than T2*-Weighted Gradient-Recalled Echo MRI for Detecting Microbleeds

Background and Purpose— We investigated the sensitivity and reliability of MRI susceptibility-weighted imaging (SWI) compared with routine MRI T2*-weighted gradient-recalled echo (GRE) for cerebral microbleed (CMB) detection. Methods— We used data from a prospective study of cerebral amyloid angiopathy (n=9; mean age, 71±8.3) and healthy non–cerebral amyloid angiopathy controls (n=22; mean age, 68±6.3). Three raters (labeled 1, 2, and 3) independently interpreted the GRE and SWI sequences (using the phase-filtered magnitude image) blinded to clinical information. Results— In 9 cerebral amyloid angiopathy cases, the raters identified 1146 total CMBs on GRE and 1432 CMBs on SWI. In 22 healthy control subjects, the raters identified ≥1 CMBs in 6/22 on GRE (total 9 CMBs) and 5/22 on SWI (total 19 CMBs). Among cerebral amyloid angiopathy cases, the reliability between raters for CMB counts was good for SWI (intraclass correlation coefficient, 0.87) but only moderate for GRE (intraclass correlation coefficient, 0.52). In controls, agreement on the presence or absence of CMBs in controls was moderate to good on both SWI (&kgr; coefficient ranged from 0.57 to 0.74 across the 3 combinations of rater pairs) and GRE (&kgr; range, 0.31 to 0.70). A review of 114 hypointensities identified as possible CMBs indicated that increased detection and reliability on SWI was related to both increased contrast and higher resolution, allowing better discrimination of CMBs from the background and better anatomic differentiation from pial vessels. Conclusions— SWI confers greater reliability as well as greater sensitivity for CMB detection compared with GRE, and should be the preferred sequence for quantifying CMB counts.

Real-time MR imaging-guided passive catheter tracking with use of gadolinium-filled catheters.

PURPOSE To test the hypothesis that real-time magnetic resonance (MR) imaging-guided passive catheter tracking is feasible with use of dilute gadolinium (Gd)-filled catheters, to determine the optimal Gd concentration required for tracking, and to measure catheter tip tracking accuracy. MATERIALS AND METHODS The authors tested a real-time, T1-weighted, two-dimensional, spoiled gradient-recalled echo MR imaging sequence suitable for tracking catheters. In a yogurt phantom, the authors placed 5-F catheters filled with 2%-12% Gd solutions. MR imaging was performed with and without use of a projection dephaser that suppressed background signal. The authors measured signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and enhancement ratio to determine the optimal Gd concentration for catheter depiction. Catheter tip tracking accuracy was measured in an acrylic phantom with use of linear regression analysis, with goodness of fit assessed statistically with the F test. RESULTS Peak catheter SNR, CNR, and enhancement ratios were obtained with 4%-6% Gd concentrations. Tip tracking accuracy was determined to be +/- 0.41 mm (R2 = 0.99; P < .0001). MR imaging reconstructions were displayed up to 3.1 frames/sec. CONCLUSIONS Accurate MR imaging-guided passive catheter tracking was feasible in real-time with use of dilute Gd-filled catheters. This technique may have application in MR imaging-guided endovascular procedures.

Reliability of Assessing Percentage of Diffusion-Perfusion Mismatch

Background and Purpose— Emergent neurovascular imaging holds promise in identifying new and optimum target populations for thrombolysis in stroke. Recent research has focused on patients with diffusion-weighted MRI (DWI)-perfusion-weighted MRI (PWI) mismatch as a marker of tissue at risk of infarction and a means to select the most suitable candidates for thrombolysis. The present study sought to estimate the reliability of assessing the percentage of DWI-PWI mismatch. Methods— Thirteen patients with acute strokes had DWI and PWI within 7 hours of symptom onset. Six raters independently created relative mean transit time (rMTT) maps and then compared them with DWI images to assess the percentage of mismatch (PWI>DWI) in 10% increments. The MR scans were reassessed by 4 raters, tracing around the lesions to calculate the volume percentage of mismatch. Results— Visual assessment had an interrater reliability of 0.68 (95% CI, 0.52 to 1.0; SEM=21.6%) and an intrarater reliability of 0.80 (95% CI, 0.47 to 1.0; SEM=16.9%). Hand-drawn assessment had an interrater reliability of 0.66 (95% CI, 0.45 to 1.0; SEM=26.2%) and an intrarater reliability of 0.94 (95% CI, 0.81 to 1.0; SEM=10.9%). Conclusions— Results from the present study suggest that quantifying mismatch by the human eye is reproducible but not reliable among observers. This raises doubts about using mismatch for clinical decision making and clinical trial enrollment.

MR perfusion and diffusion in acute ischemic stroke: Human gray and white matter have different thresholds for infarction

It is thought that gray and white matter (GM and WM) have different perfusion and diffusion thresholds for cerebral infarction in humans. We sought to determine these thresholds with voxel-by-voxel, tissue-specific analysis of coregistered acute and follow-up magnetic resonance (MR) perfusion- and diffusion-weighted imaging. Quantitative cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and apparent diffusion coefficient (ADC) maps were analyzed from nine acute stroke patients (imaging acquired within 6 h of onset). The average values of each measure were calculated for GM and WM in normally perfused tissue, the region of recovered tissue and in the final infarct. Perfusion and diffusion thresholds for infarction were determined on a patient-by-patient basis in GM and WM separately by selecting thresholds with equal sensitivities and specificities. Gray matter has higher thresholds for infarction than WM (P<0.009) for CBF (20.0 mL/100 g min in GM and 12.3 mL/100 g min in WM), CBV (2.4 mL/100 g in GM and 1.7 mL/100 g in WM), and ADC (786 × 10−6 mm2/s in GM and 708 × 10−6 mm2/s in WM). The MTT threshold for infarction in GM is lower (P = 0.014) than for WM (6.8 secs in GM and 7.1 secs in WM). A single common threshold applied to both tissues overestimates tissue at risk in WM and underestimates tissue at risk in GM. This study suggests that tissue-specific analysis of perfusion and diffusion imaging is required to accurately predict tissue at risk of infarction in acute ischemic stroke.

MR-guided angioplasty of renal artery stenosis in a pig model: a feasibility study.

PURPOSE To test the hypothesis that magnetic resonance (MR) imaging can guide the percutaneous treatment of renal artery stenosis in a pig model. MATERIALS AND METHODS Ameroid constrictors were surgically placed around six renal arteries in four pigs. After 30-36 days, all stenoses were documented by conventional x-ray aortograms. MR-guided renal angioplasty was attempted for three stenoses. For these pigs, MR angiography was performed with use of contrast-enhanced three-dimensional (3D) techniques. The authors visualized catheters by filling them with dilute 4% gadolinium and imaging with two-dimensional (2D) and 3D MR fast spoiled gradient recalled echo techniques. Under MR guidance, the authors advanced a selective catheter into the affected renal artery and crossed the stenosis with a nitinol guide wire. Angioplasty was performed with a balloon catheter filled with dilute gadolinium. Stenosis and luminal diameter measurements were compared before and after angioplasty. RESULTS After ameroid constrictor placement, four significant stenoses, one mild stenosis, and one occlusion developed. Under MR guidance, the authors achieved technical success in performing three of three (100%) attempted dilations. After MR-guided angioplasty, the mean reduction in stenosis was 35% and the mean increase in luminal diameter was 1.6 mm. CONCLUSION Use of MR guidance for the angioplasty of renal artery stenosis in pigs is feasible.

A General Description of Linear Time-Frequency Transforms and Formulation of a Fast, Invertible Transform That Samples the Continuous S-Transform Spectrum Nonredundantly

Examining the frequency content of signals is critical in many applications, from neuroscience to astronomy. Many techniques have been proposed to accomplish this. One of these, the S-transform, provides simultaneous time and frequency information similar to the wavelet transform, but uses sinusoidal basis functions to produce frequency and globally referenced phase measurements. It has shown promise in many medical imaging applications but has high computational requirements. This paper presents a general transform that describes Fourier-family transforms, including the Fourier, short-time Fourier, and S- transforms. A discrete, nonredundant formulation of this transform, as well as algorithms for calculating the forward and inverse transforms are also developed. These utilize efficient sampling of the time-frequency plane and have the same computational complexity as the fast Fourier transform. When configured appropriately, this new algorithm samples the continuous S-transform spectrum efficiently and nonredundantly, allowing signals to be transformed in milliseconds rather than days, as compared to the original S-transform algorithm. The new and efficient algorithms make practical many existing signal and image processing techniques, both in biomedical and other applications.