Aleksandra Radjenovic

Modified Look-Locker inversion recovery (MOLLI) for high-resolution T1 mapping of the heart.

A novel pulse sequence scheme is presented that allows the measurement and mapping of myocardial T1 in vivo on a 1.5 Tesla MR system within a single breath‐hold. Two major modifications of conventional Look‐Locker (LL) imaging are introduced: 1) selective data acquisition, and 2) merging of data from multiple LL experiments into one data set. Each modified LL inversion recovery (MOLLI) study consisted of three successive LL inversion recovery (IR) experiments with different inversion times. We acquired images in late diastole using a single‐shot steady‐state free‐precession (SSFP) technique, combined with sensitivity encoding to achieve a data acquisition window of <200 ms duration. We calculated T1 using signal intensities from regions of interest and pixel by pixel. T1 accuracy at different heart rates derived from simulated ECG signals was tested in phantoms. T1 estimates showed small systematic error for T1 values from 191 to 1196 ms. In vivo T1 mapping was performed in two healthy volunteers and in one patient with acute myocardial infarction before and after administration of Gd‐DTPA. T1 values for myocardium and noncardiac structures were in good agreement with values available from the literature. The region of infarction was clearly visualized. MOLLI provides high‐resolution T1 maps of human myocardium in native and post‐contrast situations within a single breath‐hold. Magn Reson Med 52:141–146, 2004.

Cardiovascular magnetic resonance and single-photon emission computed tomography for diagnosis of coronary heart disease (CE-MARC): a prospective trial.

Summary Background In patients with suspected coronary heart disease, single-photon emission computed tomography (SPECT) is the most widely used test for the assessment of myocardial ischaemia, but its diagnostic accuracy is reported to be variable and it exposes patients to ionising radiation. The aim of this study was to establish the diagnostic accuracy of a multiparametric cardiovascular magnetic resonance (CMR) protocol with x-ray coronary angiography as the reference standard, and to compare CMR with SPECT, in patients with suspected coronary heart disease. Methods In this prospective trial patients with suspected angina pectoris and at least one cardiovascular risk factor were scheduled for CMR, SPECT, and invasive x-ray coronary angiography. CMR consisted of rest and adenosine stress perfusion, cine imaging, late gadolinium enhancement, and MR coronary angiography. Gated adenosine stress and rest SPECT used 99mTc tetrofosmin. The primary outcome was diagnostic accuracy of CMR. This trial is registered at controlled-trials.com, number ISRCTN77246133. Findings In the 752 recruited patients, 39% had significant CHD as identified by x-ray angiography. For multiparametric CMR the sensitivity was 86·5% (95% CI 81·8–90·1), specificity 83·4% (79·5–86·7), positive predictive value 77·2%, (72·1–81·6) and negative predictive value 90·5% (87·1–93·0). The sensitivity of SPECT was 66·5% (95% CI 60·4–72·1), specificity 82·6% (78·5–86·1), positive predictive value 71·4% (65·3–76·9), and negative predictive value 79·1% (74·8–82·8). The sensitivity and negative predictive value of CMR and SPECT differed significantly (p<0·0001 for both) but specificity and positive predictive value did not (p=0·916 and p=0·061, respectively). Interpretation CE-MARC is the largest, prospective, real world evaluation of CMR and has established CMRs high diagnostic accuracy in coronary heart disease and CMRs superiority over SPECT. It should be adopted more widely than at present for the investigation of coronary heart disease. Funding British Heart Foundation.

Preliminary experience with medical applications of rapid prototyping by selective laser sintering

Rapid prototyping techniques, originally developed for building components from computer aided designs in the motor industry, are now being applied in medicine to build models of human anatomy from high resolution multiplanar imaging data such a computed tomography (CT). The established technique of stereolithography and the more recent selective laser sintering (SLS), both build up an object layer by layer. Models have applications in surgical planning, for the design of customised implants and for training. Preliminary experience of using the SLS technique for medical applications is described, addressing questions regarding image processing, data transfer and manufacture. Pilot models, built from nylon, included two skills (a child with craniosynoslosis and an adult with hypertetorism) and a normal femur which was modelled for use in a bioengineering test of an artificial hip. The dimensions of the models were found to be in good agreement with the CT data from which they were built-for the childs skull the difference between the model and the CT data was less than 1.0 +/- 0.5 mm in each direction. Our experience showed that, with care, a combination of existing software packages may be used for data conversion. Ideally, image data of high spatial resolution should be used. The pilot models generated sufficient clinical interest for the technique to be pursued in the orthopaedic field.

Dynamic contrast-enhanced myocardial perfusion MRI accelerated with k-t sense.

In the k‐t sensitivity encoding (k‐t SENSE) method spatiotemporal data correlations are exploited to accelerate data acquisition in dynamic MRI studies. The present study demonstrates the feasibility of applying k‐t SENSE to contrast‐enhanced myocardial perfusion MRI and using the speed‐up to increase spatial resolution. At a net acceleration factor of 3.9 (k‐t factor of 5 with 11 training profiles) accurate representations of dynamic signal intensity (SI) changes were achieved in computer simulations. In vivo, 5× k‐t SENSE was compared with 2× SENSE (identical acquisition parameters except for in‐plane spatial resolution = 1.48 × 1.48 mm2 vs. 2.64 × 2.64 mm2, respectively). In 10 volunteers no differences in myocardial SI profiles were found (relative peak enhancement = 151% vs. 149.7%, maximal upslope = 12.9%/s vs. 13.3%/s for 2× SENSE and 5× k‐t SENSE, respectively, all P > 0.05). Overall image quality was similar, but endocardial dark rim artifacts were reduced with k‐t SENSE. Signal‐to‐noise ratio (SNR) in the myocardium was greater with 5× k‐t SENSE by a factor of 1.36 ± 0.23 at peak contrast enhancement with the relative yield decreasing with increasing dynamics in the object in accordance to theory. Higher nominal acceleration factors of up to 10‐fold were shown to be feasible in computer simulations and in vivo. Magn Reson Med 58:777–785, 2007.

Mode of action of abatacept in rheumatoid arthritis patients having failed tumour necrosis factor blockade: a histological, gene expression and dynamic magnetic resonance imaging pilot study.

Objectives: Abatacept is the only agent currently approved to treat rheumatoid arthritis (RA) that targets the co-stimulatory signal required for full T-cell activation. No studies have been conducted on its effect on the synovium, the primary site of pathology. The aim of this study was to determine the synovial effect of abatacept in patients with RA and an inadequate response to tumour necrosis factor alpha (TNFα) blocking therapy. Methods: This first mechanistic study incorporated both dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and arthroscopy-acquired synovial biopsies before and 16 weeks after therapy, providing tissue for immunohistochemistry and quantitative real-time PCR analyses. Results: Sixteen patients (13 women) were studied; all had previously failed TNFα-blocking therapy. Fifteen patients completed the study. Synovial biopsies showed a small reduction in cellular content, which was significant only for B cells. The quantitative PCR showed a reduction in expression for most inflammatory genes (Wald statistic of p<0.01 indicating a significant treatment effect), with particular reduction in IFNγ of −52% (95% CI −73 to −15, p<0.05); this correlated well with MRI improvements. In addition, favourable changes in the osteoprotegerin and receptor activator of nuclear factor kappa B levels were noted. DCE–MRI showed a reduction of 15–40% in MRI parameters. Conclusion: These results indicate that abatacept reduces the inflammatory status of the synovium without disrupting cellular homeostasis. The reductions in gene expression influence bone positively and suggest a basis for the recently demonstrated radiological improvements that have been seen with abatacept treatment in patients with RA.

Cardiovascular magnetic resonance physics for clinicians: part II

There are many excellent specialised texts and articles that describe the physical principles of cardiovascular magnetic resonance (CMR) techniques. There are also many texts written with the clinician in mind that provide an understandable, more general introduction to the basic physical principles of magnetic resonance (MR) techniques and applications. There are however very few texts or articles that attempt to provide a basic MR physics introduction that is tailored for clinicians using CMR in their daily practice. This is the first of two reviews that are intended to cover the essential aspects of CMR physics in a way that is understandable and relevant to this group. It begins by explaining the basic physical principles of MR, including a description of the main components of an MR imaging system and the three types of magnetic field that they generate. The origin and method of production of the MR signal in biological systems are explained, focusing in particular on the two tissue magnetisation relaxation properties (T1 and T2) that give rise to signal differences from tissues, showing how they can be exploited to generate image contrast for tissue characterisation. The method most commonly used to localise and encode MR signal echoes to form a cross sectional image is described, introducing the concept of k-space and showing how the MR signal data stored within it relates to properties within the reconstructed image. Before describing the CMR acquisition methods in detail, the basic spin echo and gradient pulse sequences are introduced, identifying the key parameters that influence image contrast, including appearances in the presence of flowing blood, resolution and image acquisition time. The main derivatives of these two pulse sequences used for cardiac imaging are then described in more detail. Two of the key requirements for CMR are the need for data acquisition first to be to be synchronised with the subjects ECG and to be fast enough for the subject to be able to hold their breath. Methods of ECG synchronisation using both triggering and retrospective gating approaches, and accelerated data acquisition using turbo or fast spin echo and gradient echo pulse sequences are therefore outlined in some detail. It is shown how double inversion black blood preparation combined with turbo or fast spin echo pulse sequences acquisition is used to achieve high quality anatomical imaging. For functional cardiac imaging using cine gradient echo pulse sequences two derivatives of the gradient echo pulse sequence; spoiled gradient echo and balanced steady state free precession (bSSFP) are compared. In each case key relevant imaging parameters and vendor-specific terms are defined and explained.

Cine MRI using steady state free precession in the radial long axis orientation is a fast accurate method for obtaining volumetric data of the left ventricle

In this study we assessed the use of a steady state free precession (SSFP) cine sequence in a series of radially orientated long axis slices for the measurement of left ventricular volumes and mass. We validated the radial long axis approach in phantoms and ex vivo porcine hearts and applied it to normal volunteers and patients using the SSFP and turbo gradient‐echo (TGE) sequences. High quality images were obtained for analysis, and the measured volumes with radial long axis SSFP sequence correlated well with short axis TGE and SSFP volumes (r > 0.98). The best interobserver agreement for left ventricular volumes was obtained using SSFP in the long axis radial orientation (variability < 2.3%). We conclude that this combination of sequence and scan orientation has intrinsic advantages for image analysis due to the improved contrast and the avoidance of errors associated with the basal slice in the short axis orientation. J. Magn. Reson. Imaging 2001;14:685–692.

Appearance of microvascular obstruction on high resolution first-pass perfusion, early and late gadolinium enhancement CMR in patients with acute myocardial infarction

BackgroundThe presence and extent of microvascular obstruction (MO) after acute myocardial infarction can be measured by first-pass gadolinium-enhanced perfusion cardiovascular magnetic resonance (CMR) or after gadolinium injection with early or late enhancement (EGE/LGE) imaging. The volume of MO measured by these three methods may differ because contrast agent diffusion into the MO reduces its apparent extent over time. Theoretically, first-pass perfusion CMR should be the most accurate method to measure MO, but this technique has been limited by lower spatial resolution than EGE and LGE as well as incomplete cardiac coverage. These limitations of perfusion CMR can be overcome using spatio-temporal undersampling methods. The purpose of this study was to compare the extent of MO by high resolution first-pass k-t SENSE accelerated perfusion, EGE and LGE.Methods34 patients with acute ST elevation myocardial infarction, treated successfully with primary percutaneous coronary intervention (PPCI), underwent CMR within 72 hours of admission. k-t SENSE accelerated first-pass perfusion MR (7 fold acceleration, spatial resolution 1.5 mm × 1.5 mm × 10 mm, 8 slices acquired over 2 RR intervals, 0.1 mmol/kg Gd-DTPA), EGE (1-4 minutes after injection with a fixed TI of 440 ms) and LGE images (10-12 minutes after injection, TI determined by a Look-Locker scout) were acquired. MO volume was determined for each technique by manual planimetry and summation of discs methodology.Resultsk-t SENSE first-pass perfusion detected more cases of MO than EGE and LGE (22 vs. 20 vs. 14, respectively). The extent of MO imaged by first-pass perfusion (median mass 4.7 g, IQR 6.7) was greater than by EGE (median mass 2.3 g, IQR 7.1, p = 0.002) and LGE (median mass 0.2 g, IQR 2.4, p = 0.0003). The correlation coefficient between MO mass measured by first-pass perfusion and EGE was 0.91 (p < 0.001).ConclusionThe extent of MO following acute myocardial infarction appears larger on high-resolution first-pass perfusion CMR than on EGE and LGE. Given the inevitable time delay between gadolinium administration and acquisition of either EGE or LGE images, high resolution first-pass perfusion imaging may be the most accurate method to quantify MO.

Magnetic resonance imaging in the assessment of metacarpophalangeal joint disease in early psoriatic and rheumatoid arthritis

Objectives: The aim of this study was to determine whether magnetic resonance imaging (MRI)‐related entheseal changes including osteitis and extracapsular oedema could be used to differentiate between metacarpophalangeal (MCP) joint involvement in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). Methods: Twenty patients (10 each with early RA and PsA) had dynamic contrast‐enhanced MRI (DCE‐MRI) of swollen MCP joints. Synovitis and tenosynovitis was calculated using quantitative analysis including the degree and kinetics of enhancement of gadolinium diethylenetriaminepentaacetic acid (Gd‐DTPA). Periarticular bone erosion and bone oedema were scored using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) proposals. Entheseal‐related features including extracapsular soft tissue enhancement or regions of diffuse bone oedema were also evaluated. Results: MRI was not able to differentiate at the group level between both cohorts on the basis of entheseal‐related disease but a subgroup of PsA patients had diffuse extracapsular enhancement (30%) or diffuse bone oedema (20%). The RA patient group had a greater degree of MCP synovitis (p<0.0001) and tenosynovitis than PsA patients (p<0.0001). There were no significant differences in either the total number of erosions (p = 0.315) or the presence of periarticular bone oedema (p = 0.105) between the groups. Conclusion: Although conventional MRI shows evidence of an enthesitis‐associated pathology in the MCP joints in PsA, this is not sufficiently common to be of diagnostic utility.

Intra-articular primatised anti-CD4: efficacy in resistant rheumatoid knees. A study of combined arthroscopy, magnetic resonance imaging, and histology

OBJECTIVES CD4+ T cells sustain the chronic synovial inflammatory response in rheumatoid arthritis (RA). SB-210396/CE 9.1 is an anti-CD4 monoclonal antibody that has documented efficacy in RA when given intravenously. This study aimed to establish the safety and efficacy of the intra-articular administration of SB-210396/CE 9.1 compared with placebo, examining its mode of action using a combined imaging approach of arthroscopy, magnetic resonance imaging (MRI), and histology. METHODS Thirteen RA patients with active, resistant knee synovitis, were randomised to intra-articular injection of placebo (n=3), 0.4 mg (n=3) or 40 mg (n=7) of anti-CD4 after sequential dynamic gadolinium enhanced MRI, followed by same day arthroscopy and synovial membrane biopsy. Imaging and arthroscopic synovial membrane sampling were repeated at six weeks. This study used a unique region of interest (ROI) analysis mapping the MRI area analysed to the specific biopsy site identified arthroscopically, thus providing data for all three modalities at the same synovial membrane site. RESULTS 12 patients completed the study (one placebo treated patient refused further MRI). Arthroscopic improvement was observed in 0 of 2 placebo patients but in 10 of 10 patients receiving active drug (>20% in 6 of 10). Improvement in MRI was consistently observed in all patients of the 40 mg group but not in the other two groups. A reduction in SM CD4+ score was noted in the 40 mg group and in the 0.4 mg group. Strong correlations both before and after treatment, were identified between the three imaging modalities. Intra-articular delivery of SB-210396/CE 9.1 was well tolerated. CONCLUSIONS SB-210396/CE 9.1 is safe when administered by intra-articular injection. A trend toward efficacy was found by coordinated MRI, arthroscopic, and histological imaging, not seen in the placebo group. The value of ROI analysis was demonstrated.