[Anticholinergic scales: Use in psychiatry and update of the anticholinergic impregnation scale]. / Les échelles anticholinergiques : usage en psychiatrie et mise à jour de l'échelle d'imprégnation anticholinergique.

Anticholinergic properties are well known to prescribers, notably in mental health, as a therapeutic strategy for i.e. extrapyramidal syndrome but also as a source of numerous adverse side effects. Herein, we propose a narrative literature review describing: (i) cholinergic pharmacology and anticholinergic properties; (ii) the importance of anticholinergic therapeutic properties in psychiatry; (iii) the existing anticholinergic drug scales and their usage limitations in Psychiatry and; last (iv) an update to the anticholinergic drug impregnation scale, designed for the French psychiatry practice. The anticholinergic side effects can appear both in the peripheral level (dry mouth, constipation, etc.) and in the central level (especially as cognitive deficits). Many of the so called « anticholinergic ¼ drugs are in fact entirely or mostly antimuscarinic and act essentially as parasympathetic system antagonists. Overall, anticholinergic/antimuscarinic side effects are usually attributed to psychotropic medications: to certain antipsychotics, notably classical neuroleptics such as phenothiazine and also to tricyclic antidepressants. In practice, the impact of anticholinergic toxicity treatments is often highlighted due to their excessively prolonged use in patients on antipsychotics. Interestingly, these antipsychotic treatments are better known for their anticholinergic side effects, especially cognitive ones, with an early onset specially in elder patients and/or in the case of polymedication. In order to evaluate anticholinergic side effects, metrics known as anticholinergic burden scales were created in the last few decades. Nowadays, 13 different scales are documented and accepted by the international academic community, but only three of them are commonly used: the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Burden Scale (ACB). All of them are based on a similar principle, consisting of grading treatments individually, and they are normally scored from 0 - no presence of side effects - to 3 - anticholinergic effects considered to be strong or very strong. Using these scales enables the calculation of the so-called "anticholinergic burden", which corresponds to the cumulative effect of using multiple medications with anticholinergic properties simultaneously. The application of anticholinergic scales to patients with psychiatric disorders has revealed that schizophrenic patients seem to be especially sensitive to anticholinergic cognitive side effects, while elder and depressed patients were more likely to show symptoms of dementia when exposed to higher anticholinergic burden. Unfortunately, these tools appear to have a low parallel reliability, and so they might induce large differences when assessing side effects predictability. In addition, the capacity of these scales to predict central adverse effects is limited due to the fact they poorly or do not differentiate, the ability of treatments to cross the blood-brain barrier. Finally, one last limitation on the validity of these scales is prescription posology is not accounted for side effects considered to be dose dependent. Recently, the MARANTE (Muscarinic Acetylcholine Receptor ANTagonist Exposure) scale has incorporated an anticholinergic burden weighting by posology. Nevertheless, this new model can be criticized, due to the limited number of medications included and due to testing a limited number of potency ranges and dosages for each treatment. Herein, we propose an update to the Anticholinergic Impregnation Scale, developed specifically for the French Psychiatry practice. The scale validation was based on an evaluation of the prescriptions correcting anticholinergic peripheral side effects (constipation, xerostomia and xeropthalmia). This indirect evaluation allowed us to show patients with an anticholinergic impregnation score higher than 5 received significantly more treatments for constipation and xerostomia. This strategy bypasses the bias of a cognitive evaluation in patients with severe mental health disorders. Moreover, the relevance of a tool developed specifically for French psychiatry is justified by the fact that some highly prescribed treatments for mental illness in France (cyamemazine and tropatemine) are strong anticholinergics, and also by the fact they are rarely included in the existing anticholinergic scales. This update of the original scale, published in 2017, includes information whether prescribed drugs cross the blood-brain barrier and thus makes possible a more accurate assessment when evaluating anticholinergic central side effects. Finally, the anticholinergic impregnation scale will soon be integrated into a prescription help software, which is currently being developed to take into consideration dose dependent adverse effects.

Whole-Body Diffusion Imaging Applying Simultaneous Multi-Slice Excitation.

PURPOSE: The purpose of this study was to examine the feasibility of a fast protocol for whole-body diffusion-weighted imaging (WB-DWI) using a slice-accelerated echo-planar sequence, which, when using comparable image acquisition parameters, noticeably reduces measurement time compared to a conventional WB-DWI protocol. MATERIALS AND METHODS: A single-shot echo-planar imaging sequence capable of simultaneous slice excitation and acquisition was optimized for WB-DWI on a 3 T MR scanner, with a comparable conventional WB-DWI protocol serving as the reference standard. Eight healthy individuals and one oncologic patient underwent WB-DWI. Quantitative analysis was carried out by measuring the apparent diffusion coefficient (ADC) and its coefficient of variation (CV) in different organs. Image quality was assessed qualitatively by two independent radiologists using a 4-point Likert scale. RESULTS: Using our proposed protocol, the scan time of the WB-DWI measurement was reduced by up to 25.9 %. Both protocols, the slice-accelerated protocol and the conventional protocol, showed comparable image quality without statistically significant differences in the reader scores. Similarly, no significant differences of the ADC values of parenchymal organs were found, whereas ADC values of brain tissue were slightly higher in the slice-accelerated protocol. CONCLUSION: It was demonstrated that slice-accelerated DWI can be applied to WB-DWI protocols with the potential to greatly reduce the required measurement time, thereby substantially increasing clinical applicability. KEY POINTS: •Whole-body diffusion-weighted imaging (WB-DWI) using simultaneous multi-slice and blipped-CAIPIRINHA reduces the measurement time strongly without having a significant impact on image quality. •The reduction in measurement time might strongly contribute to the clinical applicability of WB-DWI. •However, further refinement of the slice-accelerated EPI sequence, and the WB-DWI protocol applying this sequence type seems necessary; and the value of such WB-DWI protocols for assessment of systemic oncological diseases needs to be investigated in further clinical studies.

Metal artefact reduction in MRI at both 1.5 and 3.0 T using slice encoding for metal artefact correction and view angle tilting.

OBJECTIVE: To compare metal artefact reduction in MRI at both 3.0 T and 1.5 T using different sequence strategies. METHODS: Metal implants of stainless steel screw and plate within agarose phantoms and tissue specimens as well as three patients with implants were imaged at both 1.5 T and 3.0 T, using view angle tilting (VAT), slice encoding for metal artefact correction with VAT (SEMAC-VAT) and conventional sequence. Artefact reduction in agarose phantoms was quantitatively assessed by artefact volume measurements. Blinded reads were conducted in tissue specimen and human imaging, with respect to artefact size, distortion, blurring and overall image quality. Wilcoxon and Friedman tests for multiple comparisons and intraclass correlation coefficient (ICC) for interobserver agreement were performed with a significant level of p < 0.05. RESULTS: Compared with conventional sequences, SEMAC-VAT significantly reduced metal artefacts by 83% ± 9% for the screw and 89% ± 3% for the plate at 1.5 T; 72% ± 7% for the screw and 38% ± 13% for the plate at 3.0 T (p < 0.05). In qualitative analysis, SEMAC-VAT allowed for better visualization of tissue structures adjacent to the implants and produced better overall image quality with good interobserver agreement for both tissue specimen and human imaging (ICC = 0.80-0.99; p < 0.001). In addition, VAT also markedly reduced metal artefacts compared with conventional sequence, but was inferior to SEMAC-VAT. CONCLUSION: SEMAC-VAT and VAT techniques effectively reduce artefacts from metal implants relative to conventional imaging at both 1.5 T and 3.0 T. ADVANCES IN KNOWLEDGE: The feasibility of metal artefact reduction with SEMAC-VAT was demonstrated at 3.0-T MR. SEMAC-VAT significantly reduced metal artefacts at both 1.5 and 3.0 T. SEMAC-VAT allowed for better visualization of the tissue structures adjacent to the metal implants. SEMAC-VAT produced consistently better image quality in both tissue specimen and human imaging.

Ankylosing spondylitis: correlations between clinical and MRI indices of sacroiliitis activity.

AIM: To analyse the correlations between clinical and MRI sacroiliitis activity indices in ankylosing spondylitis (AS). MATERIALS AND METHODS: Sixteen normal volunteers and 52 patients were enrolled. The clinical AS activity indices included the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score, serum high-sensitivity C-reactive protein, and erythrocyte sedimentation rate. The MRI sacroiliitis activity indices included apparent diffusion coefficient (ADC) values of bone and the Spondyloarthritis Research Consortium of Canada (SPARCC) score. RESULTS: The mean SPARCC score of the control group was 0 and of the AS group was 9.9 ± 9.1 (range 0-36). The mean ADC value of the AS group was statistically significantly higher than that of the control group (49.7 ± 20.2 × 10(-5)mm(2)/s versus 38.9 ± 5.3 × 10(-5)mm(2)/s, p < 0.05). The BASDAI score showed a statistically significant correlation with the SPARCC score (r = 0.685, p < 0.05) and with ADC values (r = 0.329, p < 0.05). ADC values correlated with the SPARCC score (r = 0.390, p < 0.05). CONCLUSION: ADC values and the SPARCC index may be useful activity indices in AS.

Diffusion tensor imaging in evaluation of thigh muscles in patients with polymyositis and dermatomyositis.

OBJECTIVE: To explore the diffusion tensor imaging (DTI) characteristics of thigh muscles in patients with polymyositis (PM) and dermatomyositis (DM). METHODS: 12 patients with known PM/DM and 10 healthy volunteers were enrolled in this study. Both DTI and conventional MR sequences were performed on both thighs of all subjects. Apparent diffusion coefficient (ADC), fractional anisotropy (FA) and three eigenvalues were compared between the PM/DM group and the healthy group. One-way analysis of variance and Student's t-test were used for statistical analyses with a significance of p < 0.05. RESULTS: In the healthy group, the vastus intermedius muscle showed the highest ADC value and the gracilis (GA) muscle showed the lowest ADC value. These results were statistically significant when compared with other muscles (p < 0.05). The GA, semi-tendinosus and semi-membranosus muscles showed higher FA values than the other three thigh muscles (p < 0.05). The mean ADC value and three eigenvalues of oedematous muscles in the PM/DM group were higher on average and showed a statistically significant difference when compared with unaffected (non-oedematous muscles in patients) and normal muscles (p < 0.05). There was no statistical difference in the mean FA value between oedematous and normal muscles. The mean ADC, FA and three eigenvalues in unaffected muscles (in patients) showed no statistical differences from those in normal muscles (p > 0.05). CONCLUSION: DTI can be used to quantitatively evaluate the anisotropic diffusion characteristics of muscles in patients with PM/DM. ADVANCES IN KNOWLEDGE: A new application of DTI is proposed for inflammatory myopathies. The results show that ADC and the three eigenvalues were significantly different between diseased and normal muscles, a finding of potential value in both diagnosis and treatment monitoring of myopathies.

Central nervous system: review of clinical use of contrast media.

The clinical utility of intravenous contrast administration for magnetic resonance imaging in neoplastic disease of the brain, non-neoplastic disease of the brain, and in disease of the spine is reviewed. Magnetic resonance imaging (MRI) is the modality of choice for the evaluation of most suspected intracranial and spinal pathology. Contrast use substantially improves lesion detection and differential diagnosis. Applications are discussed in neoplastic disease, infection, vascular disorders, demyelinating disease, and trauma (specifically including in the spine disk herniation). Gadolinium chelates play as important a role in magnetic resonance imaging as do iodinated agents in computed tomography. Contrast administration facilitates time-efficient and cost-effective diagnosis.

Safety of magnetic resonance contrast media.

Intravenous contrast media, specifically the gadolinium chelates, are well accepted for use in the clinical practice of magnetic resonance imaging. The gadolinium chelates are considered to be very safe and lack (in intravenous use) the nephrotoxicity found with iodinated contrast media. Minor adverse reactions, including nausea and hives, occur in a low percentage of cases. The four agents currently available in the United States cannot be differentiated on the basis of these adverse reactions. Severe anaphylactoid reactions are also known to occur with all agents, although these are uncommon. This review discusses the safety issues involved with intravenous administration of the gadolinium chelates and off-label use. The latter is common in clinical practice and permits broader application of these agents.

[Administration of MR contrast agents outside of approved indications (off-label use]. / Einsatz von MR-Kontrastmitteln ausserhalb der zugelassenen Anwendung (Off-label use).

PURPOSE: The use of MRI contrast agents outside their labeled indications is routine in radiology. However, physicians feel frequently at unease. It is the aim of this paper to introduce the medical, juridicial and billing relevant issues in order to improve the knowledge on this topic. METHODS: The basis for off-label use is the physician's prerogative, which finds its basis in the "declaration of Helsinki". RESULTS: Off-label use is allowed under special conditions and might be even the medical state of the art. CONCLUSION: The necessity for off-label use will continue to increase for MR-contrast agents, as clinical trials for registration purpose are quite costly and manufactures continuously will concentrate on the essential indications.

A clinical comparison of the safety and efficacy of MultiHance (gadobenate dimeglumine) and Omniscan (Gadodiamide) in magnetic resonance imaging in patients with central nervous system pathology.

RATIONALE AND OBJECTIVES: The safety and diagnostic efficacy of MultiHance (gadobenate dimeglumine) in the central nervous system (CNS) were evaluated in a double-blind, multicenter, phase III clinical trial. METHODS: Two hundred five patients highly suspected of having a CNS lesion (by previous imaging exam) were enrolled at 16 sites in the United States. Patients were randomized to one of three incremental dosing regimens. Magnetic resonance imaging with Omniscan (gadodiamide) at doses of 0.1 and 0.3 mmol/kg was compared with MultiHance (gadobenate dimeglumine) at doses of 0.05 and 0.15 mmol/kg and at 0.1 and 0.2 mmol/kg. RESULTS: Compared with predose images alone, efficacy was demonstrated in each of the gadobenate dimeglumine and gadodiamide groups (single and cumulative doses) as indicated by the level of diagnostic information, number of lesions detected, and contrast-to-noise ratio measurements. The level of diagnostic information from gadobenate dimeglumine at 0.1 mmol/kg was equivalent to that with gadodiamide at the same dose. One of the two blinded reviewers found equivalence between the gadobenate dimeglumine 0.05 mmol/kg dose and gadodiamide at 0.1 mmol/kg. Both reviewers found the level of diagnostic information to be equivalent after the second dose of contrast for all three dosing regimens. The cumulative doses of gadobenate dimeglumine were well tolerated and as safe as gadodiamide. CONCLUSIONS: Gadobenate dimeglumine is comparable to gadodiamide in terms of safety and efficacy for imaging of CNS lesions, with a possible advantage in imaging applications owing to enhanced T1 relaxivity.

A review of contrast media research in 1999-2000.

Contrast media research published during the years 1999 and 2000 is reviewed in this article, in terms of relevance to developments within the field of diagnostic radiology. The primary focus is on publications from the journal Investigative Radiology, which publishes much of the clinical and laboratory research performed in this field. The journals Radiology and the American Journal of Roentgenology are dominant in the field of diagnostic radiology and together publish more than 10 times the number of articles as appear each year in Investigative Radiology. However, in 1999 for example, these two journals together published fewer articles than did Investigative Radiology alone that concerned basic (animal) research with contrast media. Thirty-six percent of the articles in Investigative Radiology in 1999 had a primary focus on contrast media and 18% on basic (animal) research with contrast media. To make this review more complete, articles from other major journals are cited and discussed, as needed, to provide supplemental information in the few areas not well covered by articles in Investigative Radiology. The safety of contrast media is always an important topic and research continues to be performed in this area, both to explore fundamental issues regarding iodinated contrast media and also to establish the overall safety profile of new magnetic resonance (MR) and ultrasound agents. In regard to preclinical investigations, most of the work performed in the last 2 years has been with MR and ultrasound. In MR, research efforts continue to be focused on the development of targeted agents. In ultrasound, research efforts are split between studies looking at new imaging methods and early studies of targeted agents. In regard to the clinical application of contrast media, the published literature continues to be dominated by MR. Investigations include the study of disease in clinical trials and in animal models. A large number of studies continue to be published in regard to new techniques and applications within the field of contrast-enhanced magnetic resonance angiography. This field represents the single, largest new clinical application of contrast media in MR to emerge in the last decade. New clinical research continues to be published regarding the use of contrast media in computed tomography (CT), ultrasound, and x-ray angiography. The introduction of spiral CT (together with the multidetector scanners) has led to greater utilization of this modality, as well as intravenous iodinated contrast media. The number of publications regarding clinical applications of intravenously injected ultrasound contrast agents remains low, with the high expectations in regard to growth (in terms of number of exams using contrast) of the last decade yet to be fulfilled.

[Comparison of contrast behavior of gadobenate-dimeglumine and Gd-DTPA in intra-axial brain tumors. A double-blind randomized intraindividual cross-over study]. / Vergleich des Kontrastverhaltens von Gadobenat-Dimeglumine und Gd-DTPA bei intraaxialen Hirntumoren. Eine doppelblinde randomisierte intraindividuelle Cross-over-Studie.

The purposes of the study was to assess intra-axial brain tumors by a blinded comparison of gadobenat-dimeglumine and Gd-DTPA. 27 patients with known cerebral gliomas or metastases were included into an intra-individual randomized double-blinded cross-over study. The protocol included T1 SE, T2 FSE and after contrast a series of five T1 SE sequences followed by T1 SE with MT, T1 SE, and 3D GRE sequences. Imaging data acquired at two centers were assessed on-site by the investigators and off-site by two experienced readers using quantitative and qualitative criteria. For a quantitative analysis tumor contrast and contrast-to-noise ratios were determined out of ROI in tumor, unaffected white matter, a region outside the head, and an external reference tube. For the qualitative assessment on- and off-site readers were asked to compare both MR scans for lesion contrast, lesion delineation and information upon the internal morphology and structure. In the quantitative analysis lesions examined with gadobenat-dimeglumine present a maximal 26% increase of the lesion contrast. In both, the on-site, as well as the off-site assessment the intensity of enhancement and the lesion contrast were found to be significantly better with gadobenat-dimeglumine enhanced MRI. There was a trend towards gadobenat-dimeglumine for the delineation of the lesion from the surrounding tissue and the internal lesion morphology. Based on our observations gadobenat-dimeglumine proved to be a safe and valuable contrast media for the assessment of CNS neoplasms. Compared with Gd-DTPA it provides a more intense contrast enhancement and a better tumor contrast which might be of importance for the further management of these patients.

Multicentre dose-ranging study on the efficacy of USPIO ferumoxtran-10 for liver MR imaging.

AIM: A dose ranging multicentre phase-II clinical trial was conducted to evaluate the efficacy of ultrasmall superparamagnetic iron oxide (USPIO) ferumoxtran-10 for magnetic resonance (MR) imaging of focal hepatic lesions. MATERIAL AND METHODS: Ninety-nine patients with focal liver lesions received USPIO at a dose of 0.8 (n = 35), 1.1 (n = 32), or 1.7 (n = 32) mg Fe/kg. Liver MR imaging was performed before and after USPIO with T1-weighted and T2-weighted pulse sequences. Images were analysed by two independent readers for additional information (lesion detection, exclusion, characterization and patient management). Signal intensity (SI) based quantitative measurements were also taken. RESULTS: Post-contrast medium MR imaging showed additional information in 71/97 patients (73%) for reader one and 83/96 patients (86%) for reader two. The results with all three doses were statistically significant (P < 0.05). Signal intensity analysis revealed that all three doses increased liver SI on T1-weighted images and decreased liver SI on T2-weighted images. On T2-weighted images metastases increased in contrast relative to normal hepatic parenchyma whereas haemangiomas decreased in contrast. On T2-weighted images there was statistically improved efficacy at the intermediate dose, which did not improve at the highest dose. CONCLUSION: Ultrasmall superparamagnetic iron oxide was an effective contrast agent for liver MR imaging at all doses and a dose of 1.1 mg Fe/kg was recommended for future clinical trials.

Safety of approved MR contrast media for intravenous injection.

In the last 10 years, the use of intravenous contrast media in magnetic resonance (MR) has become well-established clinical practice. Contrast media provide critical additional diagnostic information in many instances. The gadolinium chelates constitute the largest group of MR contrast media and are considered to be very safe. These agents are thought to be safer than nonionic iodinated contrast agents. Unlike x-ray agents, the gadolinium chelates are not nephrotoxic. Minor adverse reactions, including nausea (1%-2% for all agents) and hives (<1% for all agents), occur in a very low percent of cases. Health care personnel should be aware of the (extremely uncommon) potential for severe anaphylactoid reactions in association with the use of MR contrast media and be prepared should complications arise. The four gadolinium chelates currently available worldwide, gadopentetate dimeglumine, gadoteridol, gadodiamide, and gadoterate meglumine, cannot be differentiated on the basis of adverse reactions. Far fewer patients have been examined to date with the two other agents that have widespread approval, mangafodipir trisodium and ferumoxides. These latter two agents are considered to be very safe but have a higher percentage of associated adverse reactions (7%-17% with mangafodipir trisodium and 15% with ferumoxides). This review discusses the safety issues involved with administration of intravenous contrast media in MR imaging, focusing on the six agents (four gadolinium chelates, one manganese chelate, and the last a large iron particle) with widespread use world-wide.

Phase II double-blind, dose-ranging clinical evaluation of gadobenate dimeglumine in focal liver lesions: with analysis of liver and kidney signal change on early and delayed imaging.

To evaluate the effect of contrast dose using gadobenate dimeglumine, 30 patients with focal liver lesions documented by computed tomography or ultrasound were studied by magnetic resonance imaging at 1.5 T. Patients received one of four doses of gadobenate dimeglumine (0.025, 0.05, 0.1, or 0.2 mmol/kg) or saline. The order of dosage was randomized, with both the physician and patient blinded to the administered dose. Scans were obtained before, immediately following injection, and after 80 minutes of delay. Enhancement effects were quantified by region of interest measurements. Films were also reviewed in a randomized prospective fashion by an abdominal radiologist blinded to contrast dose and diagnosis. Higher doses led to a statistically significant improvement in enhancement of normal liver, both on immediate (P = 0.01 for the comparison of 0.1 and 0.2 mmol/kg immediately post-contrast) and delayed scans (P = 0.003 for the same comparison). Liver-lesion contrast-to-noise ratio also increased with dose, although results for most comparisons by dose were not statistically significant. Scans following gadobenate dimeglumine injection were judged to provide additional diagnostic confidence sufficient to affect patient management in 10 of 24 cases. In seven cases this information was provided by dynamic scans, in one case by delayed scans, and in two cases by both dynamic and delayed scans. In 2 of the 10 cases the dose was 0.025 mmol/kg, in 2 cases 0.05 mmol/kg, in 3 cases 0.1 mmol/kg, and in 3 cases 0.2 mmol/kg. Gadobenate dimeglumine is effective for imaging of focal liver lesions at a range of doses, with trends toward improved diagnostic information at higher doses.