Increase of [(18)F]FLT tumor uptake in vivo mediated by FdUrd: toward improving cell proliferation positron emission tomography.

PURPOSE: 3'-deoxy-3'-[(18)F]fluorothymidine ([(18)F]FLT), a cell proliferation positron emission tomography (PET) tracer, has been shown in numerous tumors to be more specific than 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG) but less sensitive. We studied the capacity of a nontoxic concentration of 5-fluoro-2'-deoxyuridine (FdUrd), a thymidine synthesis inhibitor, to increase uptake of [(18)F]FLT in tumor xenografts. METHODS: The duration of the FdUrd effect in vivo on tumor cell cycling and thymidine analogue uptake was studied by varying FdUrd pretreatment timing and holding constant the timing of subsequent flow cytometry and 5-[(125)I]iodo-2'-deoxyuridine biodistribution measurements. In [(18)F]FLT studies, FdUrd pretreatment was generally performed 1 h before radiotracer injection. [(18)F]FLT biodistributions were measured 1 to 3 h after radiotracer injection of mice grafted with five different human tumors and pretreated or not with FdUrd and compared with [(18)F]FDG tumor uptake. Using microPET, the dynamic distribution of [(18)F]FLT was followed for 1.5 h in FdUrd pretreated mice. High-field T2-weighted magnetic resonance imaging (MRI) and histology were used comparatively in assessing tumor viability and proliferation. RESULTS: FdUrd induced an immediate increase in tumor uptake of 5-[(125)I]iodo-2'-deoxyuridine, that vanished after 6 h, as also confirmed by flow cytometry. Biodistribution measurements showed that FdUrd pretreatment increased [(18)F]FLT uptake in all tumors by factors of 3.2 to 7.8 compared with controls, while [(18)F]FDG tumor uptake was about fourfold and sixfold lower in breast cancers and lymphoma. Dynamic PET in FdUrd pretreated mice showed that [(18)F]FLT uptake in all tumors increased steadily up to 1.5 h. MRI showed a well-vascularized homogenous lymphoma with high [(18)F]FLT uptake, while in breast cancer, a central necrosis shown by MRI was inactive in PET, consistent with the histomorphological analysis. CONCLUSION: We showed a reliable and significant uptake increase of [(18)F]FLT in different tumor xenografts after low-dose FdUrd pretreatment. These results show promise for a clinical application of FdUrd aimed at increasing the sensitivity of [(18)F]FLT PET.

Imaging for clarification of accusation of treatment error

In the assessment of medical malpractice imaging methods can be used for the documentation of crucial morphological findings which are indicative for or against an iatrogenically caused injury. The clarification of deaths in this context can be usefully supported by postmortem imaging (primarily native computed tomography, angiography, magnetic resonance imaging). Postmortem imaging offers significant additional information compared to an autopsy in the detection of iatrogenic air embolisms and documentation of misplaced medical aids before dissection with an inherent danger of relocation. Additional information is supplied by postmortem imaging in the search for sources of bleeding as well as the documentation of perfusion after cardiovascular surgery. Key criteria for the decision to perform postmortem imaging can be obtained from the necessary preliminary inspection of clinical documentation.

MP2RAGE, a self bias-field corrected sequence for improved segmentation and T1-mapping at high field.

The large spatial inhomogeneity in transmit B(1) field (B(1)(+)) observable in human MR images at high static magnetic fields (B(0)) severely impairs image quality. To overcome this effect in brain T(1)-weighted images, the MPRAGE sequence was modified to generate two different images at different inversion times, MP2RAGE. By combining the two images in a novel fashion, it was possible to create T(1)-weighted images where the result image was free of proton density contrast, T(2) contrast, reception bias field, and, to first order, transmit field inhomogeneity. MP2RAGE sequence parameters were optimized using Bloch equations to maximize contrast-to-noise ratio per unit of time between brain tissues and minimize the effect of B(1)(+) variations through space. Images of high anatomical quality and excellent brain tissue differentiation suitable for applications such as segmentation and voxel-based morphometry were obtained at 3 and 7 T. From such T(1)-weighted images, acquired within 12 min, high-resolution 3D T(1) maps were routinely calculated at 7 T with sub-millimeter voxel resolution (0.65-0.85 mm isotropic). T(1) maps were validated in phantom experiments. In humans, the T(1) values obtained at 7 T were 1.15+/-0.06 s for white matter (WM) and 1.92+/-0.16 s for grey matter (GM), in good agreement with literature values obtained at lower spatial resolution. At 3 T, where whole-brain acquisitions with 1 mm isotropic voxels were acquired in 8 min, the T(1) values obtained (0.81+/-0.03 s for WM and 1.35+/-0.05 for GM) were once again found to be in very good agreement with values in the literature.

Guidelines for imaging retinoblastoma: imaging principles and MRI standardization.

Retinoblastoma is the most common intraocular tumor in children. The diagnosis is usually established by the ophthalmologist on the basis of fundoscopy and US. Together with US, high-resolution MRI has emerged as an important imaging modality for pretreatment assessment, i.e. for diagnostic confirmation, detection of local tumor extent, detection of associated developmental malformation of the brain and detection of associated intracranial primitive neuroectodermal tumor (trilateral retinoblastoma). Minimum requirements for pretreatment diagnostic evaluation of retinoblastoma or mimicking lesions are presented, based on consensus among members of the European Retinoblastoma Imaging Collaboration (ERIC). The most appropriate techniques for imaging in a child with leukocoria are reviewed. CT is no longer recommended. Implementation of a standardized MRI protocol for retinoblastoma in clinical practice may benefit children worldwide, especially those with hereditary retinoblastoma, since a decreased use of CT reduces the exposure to ionizing radiation.

Inherently self-calibrating non-Cartesian parallel imaging.

The use of self-calibrating techniques in parallel magnetic resonance imaging eliminates the need for coil sensitivity calibration scans and avoids potential mismatches between calibration scans and subsequent accelerated acquisitions (e.g., as a result of patient motion). Most examples of self-calibrating Cartesian parallel imaging techniques have required the use of modified k-space trajectories that are densely sampled at the center and more sparsely sampled in the periphery. However, spiral and radial trajectories offer inherent self-calibrating characteristics because of their densely sampled center. At no additional cost in acquisition time and with no modification in scanning protocols, in vivo coil sensitivity maps may be extracted from the densely sampled central region of k-space. This work demonstrates the feasibility of self-calibrated spiral and radial parallel imaging using a previously described iterative non-Cartesian sensitivity encoding algorithm.

Sex differences in the neurobiology of fear conditioning and extinction: a preliminary fMRI study of shared sex differences with stress-arousal circuitry.

BACKGROUND: The amygdala, hippocampus, medial prefrontal cortex (mPFC) and brain-stem subregions are implicated in fear conditioning and extinction, and are brain regions known to be sexually dimorphic. We used functional magnetic resonance imaging (fMRI) to investigate sex differences in brain activity in these regions during fear conditioning and extinction. METHODS: Subjects were 12 healthy men comparable to 12 healthy women who underwent a 2-day experiment in a 3 T MR scanner. Fear conditioning and extinction learning occurred on day 1 and extinction recall occurred on day 2. The conditioned stimuli were visual cues and the unconditioned stimulus was a mild electric shock. Skin conductance responses (SCR) were recorded throughout the experiment as an index of the conditioned response. fMRI data (blood-oxygen-level-dependent [BOLD] signal changes) were analyzed using SPM8. RESULTS: Findings showed no significant sex differences in SCR during any experimental phases. However, during fear conditioning, there were significantly greater BOLD-signal changes in the right amygdala, right rostral anterior cingulate (rACC) and dorsal anterior cingulate cortex (dACC) in women compared with men. In contrast, men showed significantly greater signal changes in bilateral rACC during extinction recall. CONCLUSIONS: These results indicate sex differences in brain activation within the fear circuitry of healthy subjects despite similar peripheral autonomic responses. Furthermore, we found that regions where sex differences were previously reported in response to stress, also exhibited sex differences during fear conditioning and extinction.

Imaging of the unstable plaque: how far have we got?

Rupture of unstable plaques may lead to myocardial infarction or stroke and is the leading cause of morbidity and mortality in western countries. Thus, there is a clear need for identifying these vulnerable plaques before the rupture occurs. Atherosclerotic plaques are a challenging imaging target as they are small and move rapidly, especially in the coronary tree. Many of the currently available imaging tools for clinical use still provide minimal information about the biological characteristics of plaques, because they are limited with respect to spatial and temporal resolution. Moreover, many of these imaging tools are invasive. The new generation of imaging modalities such as magnetic resonance imaging, nuclear imaging such as positron emission tomography and single photon emission computed tomography, computed tomography, fluorescence imaging, intravascular ultrasound, and optical coherence tomography offer opportunities to overcome some of these limitations. This review discusses the potential of these techniques for imaging the unstable plaque.

Coronary MR angiography clinical applications and potential for imaging coronary artery disease.

Over the past decade, CMRA has emerged as a unique clinical imaging tool with applications in selected populations. Patients with suspected coronary artery anomalies and patients with Kawasaki disease and coronary aneurysms are among those for whom CMRA has demonstrated clinical usefulness. For assessment of patients with atherosclerotic CAD, CMRA is useful for detection of patency of bypass grafts. At centers with appropriate expertise and resources, CMRA also appears to be of value for exclusion of severe proximal multivessel CAD in selected patients. Data from multicenter trials will continue to define the clinical role of CMRA, particularly as it relates to assessment of CAD. Future developments and enhancements of CMRA promise better lumen and coronary artery wall imaging. This may become the new target in noninvasive evaluation of CAD.

Postmortem imaging of sudden cardiac death

Postmortem imaging is increasingly used in forensic practice in cases of natural deaths related to cardiovascular diseases, which represent the most common causes of death in developed countries. While radiological examination is generally considered to be a good complement for conventional autopsy, it was thought to have limited application in cardiovascular pathology. At present, multidetector computed tomography (MDCT), CT angiography, and cardiac magnetic resonance imaging (MRI) are used in postmortem radiological investigation of cardiovascular pathologies. This review presents the actual state of postmortem imaging for cardiovascular pathologies in cases of sudden cardiac death (SCD), taking into consideration both the advantages and limitations. The radiological evaluation of ischemic heart disease (IHD), the most frequent cause of SCD in the general population of industrialized countries, includes the examination of the coronary arteries and myocardium. Postmortem CT angiography (PMCTA) is very useful for the detection of stenoses and occlusions of coronary arteries but less so for the identification of ischemic myocardium. MRI is the method of choice for the radiological investigation of the myocardium in clinical practice, but its accessibility and application are still limited in postmortem practice. There are very few reports implicating postmortem radiology in the investigation of other causes of SCD, such as cardiomyopathies, coronary artery abnormalities, and valvular pathologies. Cardiomyopathies representing the most frequent cause of SCD in young athletes cannot be diagnosed by echocardiography, the most widely available technique in clinical practice for the functional evaluation of the heart and the detection of cardiomyopathies. PMCTA and MRI have the potential to detect advanced stages of diseases when morphological substrate is present, but these methods have yet to be sufficiently validated for postmortem cases. Genetically determined channelopathies cannot be detected radiologically. This review underlines the need to establish the role of postmortem radiology in the diagnosis of SCD.

Direct MR arthrography of the shoulder under axial traction: Feasibility study to evaluate the superior labrum-biceps tendon complex and articular cartilage.

PURPOSE: To assess the value of adding axial traction to direct MR arthrography of the shoulder, in terms of subacromial and glenohumeral joint space widths, and coverage of the superior labrum-biceps tendon complex and articular cartilage by contrast material. MATERIALS AND METHODS: Twenty-one patients investigated by direct MR arthrography of the shoulder were prospectively included. Studies were performed with a 3 Tesla (T) unit and included a three-dimensional isotropic fat-suppressed T1-weighted gradient-recalled echo sequence, without and with axial traction (4 kg). Two radiologists independently measured the width of the subacromial, superior, and inferior glenohumeral joint spaces. They subsequently rated the amount of contrast material around the superior labrum-biceps tendon complex and between glenohumeral cartilage surfaces, using a three-point scale: 0 = no, 1 = partial, 2 = full. RESULTS: Under traction, the subacromial (Δ = 2.0 mm, P = 0.0003), superior (Δ = 0.7 mm, P = 0.0001) and inferior (Δ = 1.4 mm, P = 0.0006) glenohumeral joint space widths were all significantly increased, and both readers noted significantly more contrast material around the superior labrum-biceps tendon complex (P = 0.014), and between the superior (P = 0.001) and inferior (P = 0.025) glenohumeral cartilage surfaces. CONCLUSION: Direct MR arthrography of the shoulder under axial traction increases subacromial and glenohumeral joint space widths, and prompts better coverage of the superior labrum-biceps tendon complex and articular cartilage by contrast material. J. Magn. Reson. Imaging 2013;37:1228-1233. © 2012 Wiley Periodicals, Inc.

Renal tissue oxygenation in essential hypertension and chronic kidney disease.

Animal studies suggest that renal tissue hypoxia plays an important role in the development of renal damage in hypertension and renal diseases, yet human data were scarce due to the lack of noninvasive methods. Over the last decade, blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), detecting deoxyhemoglobin in hypoxic renal tissue, has become a powerful tool to assess kidney oxygenation noninvasively in humans. This paper provides an overview of BOLD-MRI studies performed in patients suffering from essential hypertension or chronic kidney disease (CKD). In line with animal studies, acute changes in cortical and medullary oxygenation have been observed after the administration of medication (furosemide, blockers of the renin-angiotensin system) or alterations in sodium intake in these patient groups, underlining the important role of renal sodium handling in kidney oxygenation. In contrast, no BOLD-MRI studies have convincingly demonstrated that renal oxygenation is chronically reduced in essential hypertension or in CKD or chronically altered after long-term medication intake. More studies are required to clarify this discrepancy and to further unravel the role of renal oxygenation in the development and progression of essential hypertension and CKD in humans.

Rôle de l'imagerie dans le diagnostic et le suivi de la polyarthrite rhumatoïde [Role of imaging in the diagnosis and follow-up of rheumatoid arthritis].

Cross-sectional imaging techniques such as magnetic resonance imaging and ultrasound are becoming essential tools not only for making an early diagnosis of rheumatoid arthritis, but also to help clarify the prognosis of the disease and better assess the response to various therapies. This article summarises the recommendations established in 2013 by the European League Against Rheumatism on the role of imaging in the diagnosis and follow-up of rheumatoid arthritis, while adding comments and emphasising on our Swiss experience with the use of ultrasound.

Use of 2D Sensitivity Encoding for Slow-Infusion Contrast-Enhanced Isotropic 3-T Whole-Heart Coronary MR Angiography.

OBJECTIVE. The purpose of this study was to improve the blood-pool signal-to-noise ratio (SNR) and blood-myocardium contrast-to-noise ratio (CNR) of slow-infusion 3-T whole-heart coronary MR angiography (MRA).SUBJECTS AND METHODS. In 2D sensitivity encoding (SENSE), the number of acquired k-space lines is reduced, allowing less radiofrequency excitation per cardiac cycle and a longer TR. The former can be exploited for signal enhancement with a higher radiofrequency excitation angle, and the latter leads to noise reduction due to lower data-sampling bandwidth. Both effects contribute to SNR gain in coronary MRA when spatial and temporal resolution and acquisition time remain identical. Numeric simulation was performed to select the optimal 2D SENSE pulse sequence parameters and predict the SNR gain. Eleven patients underwent conventional unenhanced and the proposed 2D SENSE contrast-enhanced coronary MRA acquisition. Blood-pool SNR, blood-myocardium CNR, visible vessel length, vessel sharpness, and number of side branches were evaluated.RESULTS. Consistent with the numeric simulation, using 2D SENSE in contrast-enhanced coronary MRA resulted in significant improvement in aortic blood-pool SNR (unenhanced vs contrast-enhanced, 37.5 +/- 14.7 vs 121.3 +/- 44.0; p < 0.05) and CNR (14.4 +/- 6.9 vs 101.5 +/- 40.8; p < 0.05) in the patient sample. A longer length of left anterior descending coronary artery was visualized, but vessel sharpness, coronary artery coverage, and image quality score were not improved with the proposed approach.CONCLUSION. In combination with contrast administration, 2D SENSE was found effective in improving SNR and CNR in 3-T whole-heart coronary MRA. Further investigation of cardiac motion compensation is necessary to exploit the SNR and CNR advantages and to achieve submillimeter spatial resolution.

Investigating mineralocorticoid hypertension.

About 3% of our hypertensive patients have high blood pressure induced by corticosteroids. Muscle weakness, tiredness, polyuria and polydipsia may indicate hypokalaemia. Hypokalaemic hypertension in the presence of a low plasma renin activity is the typical finding of corticosteroid hypertension. The most frequent cause of corticosteroid hypertension is primary aldosteronism (Conn's syndrome) due to an adrenal adenoma or bilateral hyperplasia of the adrenal glands. The plasma concentration of aldosterone and the ratio between plasma aldosterone and renin concentrations are high, and the kaliuresis exceeds 30 mmol/24 h in the presence of hypokalaemia. Adrenal carcinomas are rare and very malignant. The localization of an adrenal tumour is made by computer tomography (CT-scan) or nuclear magnetic resonance imaging and by measurement of the aldosterone/cortisol concentrations in the adrenal venous blood. Adenomas are removed under laparoscopy, and adrenal hyperplasias are treated with spironolactone (50-400 mg daily) or amiloride (5-30 mg daily). In rare cases (<1%), excessive stimulation of the mineralocorticoid receptor is due to cortisol (apparent mineralocorticoid excess, Cushing's disease, liquorice, or hereditary deficiency of 11beta-hydroxysteroid dehydrogenase) or to a chimeric gene coding for 11beta-hydroxylase (CYP11B1/CYP11B2). In these rare cases, the synthesis of aldosterone is under the control of the adrenocorticotrophic hormone, so treatment with glucocorticoids (dexamethasone 0.25-1.0 mg daily) is therefore possible (glucocorticoid-remediable aldosteronism). Excessive deoxycorticosterone (DOC) causes the same symptoms and signs as hyperaldosteronism. Excessive DOC is found in patients with adrenal tumours that secrete DOC, in those with hereditary or acquired disorders with dysfunctioning glucocorticoid receptors, or in those with congenital hyperplasia of the adrenal glands (deficiency of 17alpha-hydroxylase or 11beta-hydroxylase). Liddle's syndrome is a constitutive hyperactivity of the transepithelial transport of sodium, which under normal conditions is controlled by the mineralocorticoid receptor. Plasma renin and aldosterone concentrations are suppressed and the plasma potassium concentration may be normal. In contrast, plasma aldosterone and renin concentrations are increased in patients with hypokalaemic hypertension which represents secondary aldosteronism. The increased aldosterone is the consequence of stimulated renin activity due to renal or renovascular or other disorders, antihypertensive drugs or other medications. In conclusion, a work-up for corticosteroid-induced hypertension is indicated in patients with hypokalaemic hypertension and in those with severe hypertension even in the absence of hypokalaemia, and in hypertensive patients with a family history of cardiovascular diseases.