Quantitative muscle mass biomarkers are independent prognosis factors in primary central nervous system lymphoma: The role of L3-skeletal muscle index and temporal muscle thickness.

OBJECTIVE: To investigate the role of quantitative muscle biomarkers assessed with skeletal muscle index at the third lumbar vertebra (L3-SMI) and temporal muscle thickness (TMT) in predicting progression-free and overall survival in patients with primary central nervous system lymphoma (PCNSL) undergoing first-line high-dose methotrexate-based chemotherapy. METHODS: L3-SMI and TMT were calculated on abdominal CT and brain high-resolution 3D-T1-weighted MR images, respectively, using predefined validated methods. Standardized sex-specific cut-off values were used to divide patients in different risk categories. Kaplan-Meier plots were calculated, and survival analysis was performed using log-rank tests, univariate, and multivariable Cox-regression models, calculating hazard ratios (HR) and 95% confidence intervals (CI), also adjusting for potential confounders (age, sex, and performance status). RESULTS: Forty-three patients were included in this study. Median follow-up was 23 months (interquartile range 12-40); at median follow-up, rates of progression-free and overall survival for the cohort were 46% and 57%, respectively. Thirteen (30%) and 11 (26%) patients showed L3-SMI or TMT values below the predefined cut-offs. In Cox-regression multivariable analysis patients with low L3-SMI or TMT showed significantly worse progression-free (HR 4.40, 95% CI 1.66-11.61, p = 0.003; HR 4.40, 95% CI 1.68-11.49, p = 0.003, respectively) and overall survival (HR 3.16, 95% CI 1.09-9.11, p = 0.034; HR 4.93, 95% CI 1.78-13.65, p = 0.002, respectively) compared to patients with high L3-SMI or TMT. CONCLUSIONS: Quantitative muscle mass evaluation assessed by both L3-SMI and TMT is a promising tool to identify PCNSL patients at high risk of negative outcome. Confirmatory studies on larger independent series are warranted.

Comparison of T1 mapping and fixed T1 method for dynamic contrast-enhanced MRI perfusion in brain gliomas.

OBJECTIVES: To compare dynamic contrast-enhanced MRI (DCE-MRI) data obtained using different prebolus T1 values in glioma grading and molecular profiling. METHODS: We retrospectively reviewed 83 cases of gliomas: 46 lower-grade gliomas (LGG; grades II and III) and 37 high-grade gliomas (HGG; grade IV). DCE-MRI maps of plasma volume fraction (Vp), extravascular-extracellular volume fraction (Ve), and tracer transfer constant from plasma to tissue (Ktrans) were obtained using a fixed T1 value of 1400 ms and a measured T1 obtained with variable flip angle (VFA). Tumour segmentations were performed and first-order histogram parameters were extracted from volumes of interest (VOIs) after co-registration with the perfusion maps. The two methods were compared using Wilcoxon matched-pairs signed-rank test and Bland-Altman analysis. Diagnostic accuracy was obtained and compared using ROC curve analysis and DeLong's test. RESULTS: Perfusion parameters obtained with the fixed T1 value were significantly higher than those obtained with the VFA. As regards diagnostic accuracy, there were no significant differences between the two methods both for glioma grading and molecular classification, except for few parameters of both methods. CONCLUSIONS: DCE-MRI data obtained with different prebolus T1 are not comparable and the definition of a prebolus T1 by T1 mapping is not mandatory since it does not improve the diagnostic accuracy of DCE-MRI. KEY POINTS: • DCE-MRI data obtained with different prebolus T1 are significantly different, thus not comparable. • The definition of a prebolus T1 by T1 mapping is not mandatory since it does not improve the diagnostic accuracy of DCE-MRI for glioma grading. • The use of a fixed T1 value represents a valid alternative to T1 mapping for DCE-MRI analysis.

Open-Source Wax RepRap 3-D Printer for Rapid Prototyping Paper-Based Microfluidics.

The open-source release of self-replicating rapid prototypers (RepRaps) has created a rich opportunity for low-cost distributed digital fabrication of complex 3-D objects such as scientific equipment. For example, 3-D printable reactionware devices offer the opportunity to combine open hardware microfluidic handling with lab-on-a-chip reactionware to radically reduce costs and increase the number and complexity of microfluidic applications. To further drive down the cost while improving the performance of lab-on-a-chip paper-based microfluidic prototyping, this study reports on the development of a RepRap upgrade capable of converting a Prusa Mendel RepRap into a wax 3-D printer for paper-based microfluidic applications. An open-source hardware approach is used to demonstrate a 3-D printable upgrade for the 3-D printer, which combines a heated syringe pump with the RepRap/Arduino 3-D control. The bill of materials, designs, basic assembly, and use instructions are provided, along with a completely free and open-source software tool chain. The open-source hardware device described here accelerates the potential of the nascent field of electrochemical detection combined with paper-based microfluidics by dropping the marginal cost of prototyping to nearly zero while accelerating the turnover between paper-based microfluidic designs.

Contribution of magnetic resonance imaging to the diagnosis and monitoring of multiple sclerosis.

Magnetic resonance (MR) imaging is an extremely sensitive modality for detecting focal changes to the white matter (WM) in patients with multiple sclerosis (MS). For this reason, it has become an integral part of the diagnostic workup of patients with clinically isolated syndromes who are at risk of developing definite MS, and it is always recommended in patients with definite MS to confirm the diagnosis and monitor the disease course. Crucial to the use of MR imaging for diagnostic purposes is the identification of lesion features - in terms of site, shape and size - that may be considered suggestive or typical for MS, and thus help in the differential diagnosis with other neurological diseases with similar clinical presentation to MS. This need has led to the publication of several guidelines for characterising MS lesions on both dual-echo (T2 and proton density) and T1-weighted sequences after administration of contrast material. Developments in clinical research into MS have highlighted the need to formulate a diagnosis as far as possible on the basis of objective and reproducible criteria. Currently, when making a clinical diagnosis and monitoring patients with suspected MS, neurologists and neuroradiologists make use of specific diagnostic criteria that have changed over the years and will probably continue to be updated. It is therefore crucial for radiologists to become familiar with these criteria in order to improve the quality of their diagnostic assessment. In patients with a definite diagnosis of MS, on the other hand, the main problem is to define standard procedures for monitoring the course of the disease and response to pharmacological treatments. even though no guidelines currently exist, it is possible to suggest some strategies to improve the assessment in this setting.

Does higher gadolinium concentration play a role in the morphologic assessment of brain tumors? Results of a multicenter intraindividual crossover comparison of gadobutrol versus gadobenate dimeglumine (the MERIT Study).

BACKGROUND AND PURPOSE: Gadobenate dimeglumine has proved advantageous compared with other gadolinium-based contrast agents for contrast-enhanced brain MR imaging. Gadobutrol is a more highly concentrated agent (1.0 mol/L). This study intraindividually compared 0.1-mmol/kg doses of these agents for qualitative and quantitative evaluation of brain tumors. MATERIALS AND METHODS: Adult patients with suspected or known brain tumors underwent 2 identical MR imaging examinations at 1.5T, 1 with gadobenate dimeglumine and the other with gadobutrol, both at a dose of 0.1-mmol/kg body weight. The agents were injected in randomized order separated by 3-14 days. Imaging sequences and acquisition timing were identical for the 2 examinations. Three blinded readers evaluated images qualitatively for diagnostic information (lesion extent, delineation, morphology, enhancement, global preference) and quantitatively for CNR and LBR. RESULTS: One hundred fourteen of 123 enrolled patients successfully underwent both examinations. Final diagnoses were intra-axial tumors, metastases, extra-axial tumors, "other" tumors, and "nontumor" (49, 46, 8, 7, and 4 subjects, respectively). Readers 1, 2, and 3 demonstrated preference for gadobenate dimeglumine in 46 (40.7%), 54 (47.4%), and 49 (43.0%) patients, respectively, compared with 6, 7, and 7 patients for gadobutrol (P < .0001, all readers). Highly significant (P < .0001, all readers) preference for gadobenate dimeglumine was demonstrated for all other qualitative end points. Inter-reader agreement was good for all evaluations (κ = 0.414-0.629). Significantly superior CNR and LBR were determined for gadobenate dimeglumine (P < .019, all readers). CONCLUSIONS: Significantly greater morphologic information and lesion enhancement are achieved on brain MR imaging with 0.1-mmol/kg gadobenate dimeglumine compared with gadobutrol at an equivalent dose.

MR imaging of neoplastic central nervous system lesions: review and recommendations for current practice.

MR imaging is the preferred technique for the diagnosis, treatment planning, and monitoring of patients with neoplastic CNS lesions. Conventional MR imaging, with gadolinium-based contrast enhancement, is increasingly combined with advanced, functional MR imaging techniques to offer morphologic, metabolic, and physiologic information. This article provides updated recommendations to neuroradiologists, neuro-oncologists, neurosurgeons, and radiation oncologists on the practical applications of MR imaging of neoplastic CNS lesions in adults, with particular focus on gliomas, based on a review of the clinical trial evidence and personal experiences shared at a recent international meeting of experts in neuroradiology, neuro-oncology, neurosurgery, and radio-oncology.

MR imaging in multiple sclerosis: review and recommendations for current practice.

MR imaging is widely used for the diagnosis and monitoring of patients with MS. Applications and protocols for MR imaging continue to evolve, prompting a need for continual reassessments of the optimal use of this technique in clinical practice. This article provides updated recommendations on the use of MR imaging in MS, based on a review of the trial evidence and personal experiences shared at a recent expert meeting of radiologists and neurologists.

Follow-up of coiled cerebral aneurysms at 3T: comparison of 3D time-of-flight MR angiography and contrast-enhanced MR angiography.

BACKGROUND AND PURPOSE: Our aim was to compare contrast-enhanced MR angiography (CE-MRA) and 3D time-of-flight (TOF) MRA at 3T for follow-up of coiled cerebral aneurysms. MATERIALS AND METHODS: Fifty-two patients treated with Guglielmi detachable coils for 54 cerebral aneurysms were evaluated at 3T MRA. 3D TOF MRA (TR/TE = 23/3.5; SENSE factor = 2.5) and CE-MRA by using a 3D ultrafast gradient-echo sequence (TR/TE = 5.9/1.8; SENSE factor = 3) enhanced with 0.1-mmol/kg gadobenate dimeglumine were performed in the same session. Source images, 3D maximum intensity projection, 3D shaded surface display, and/or 3D volume-rendered reconstructions were evaluated in terms of aneurysm occlusion/patency and artifact presence. RESULTS: In terms of clinical classification, the 2 MRA sequences were equivalent for 53 of the 54 treated aneurysms: 21 were considered fully occluded, whereas 16 were considered to have a residual neck and 16 were considered residually patent at follow-up MRA. The remaining aneurysm appeared fully occluded at TOF MRA but had a residual patent neck at CE-MRA. Visualization of residual aneurysm patency was significantly (P = .001) better with CE-MRA compared with TOF MRA for 10 (31.3%) of the 32 treated aneurysms considered residually patent with both sequences. Coil artifacts were present in 5 cases at TOF MRA but in none at CE-MRA. No relationship was apparent between the visualization of patency and either the size of the aneurysm or the interval between embolization and follow-up. CONCLUSION: At follow-up MRA at 3T, unenhanced TOF and CE-MRA sequences are similarly effective at classifying coiled aneurysms as occluded or residually patent. However, CE-MRA is superior to TOF MRA for visualization of residual patency and is associated with fewer artifacts.

Neuroradiologic differential diagnosis of cerebral intraparenchymal hemorrhage.

Cerebral intraparenchymal hematoma (IH) is one of the most common causes of sudden onset of focal neurologic deficit. This is particularly true in the acute phase, in which IH appears hyperdense compared to the cerebral tissue. By three to four weeks, it becomes isodense with the cerebral gray matter and hypodense within 2 to 6 months. After contrast media administration, IH shows a peripheral ring of enhancement owing to the breakdown of the blood brain barrier. On magnetic resonance imaging (MRI), the appearance of IH depends upon the paramagnetic effects of the different derivates of hemoglobin and both the magnetic field strength and type of sequences used. In the hyperacute phase, IH appears hyperintense on T2 and hypointense on T1 owing to the presence of oxyhemoglobin. In the acute phase, IH is hypointense on T2 and iso-hypointense on T1 as a consequence of the presence of deoxyhemoglobin, which is converted into methemoglobin by 3 to 5 days. Methemoglobin has a strong paramagnetic effect, so in this phase IH becomes hyperintense on T1 and hypointense on T2. After 2 weeks, methemoglobin is converted in hemosiderin, responsible of the ring of hypointensity surrounding the lesion on T2WI. When an IH has been diagnosed, someone should think about the origin of bleeding. Among the different differential diagnosis, one should think about the possible origin, taking into account some parameters, such as: anamnestic data, site of the lesion, number of lesions, appearance on CT and MRI, and presence of perilesional edema. Computed tomography is a reliable and very fast tool for the diagnosis of IH, but MRI is able to provide additional information about the spontaneous or secondary nature of the hematoma, thus allowing a better characterization of the hemorrhagic lesion.

Primary brain CD30+ ALK1+ anaplastic large cell lymphoma ('ALKoma'): the first case with a combination of 'not common' variants.

BACKGROUND: Primary central nervous system lymphomas (PCNSLs) are rare tumors, mostly represented by diffuse large B cells. PCNSLs with a T phenotype are less frequently reported; even rarer are anaplastic large cell lymphomas (ALCLs). PCNSL ALCLs are commonly represented, like their systemic counterpart, by a variably prevalent amount of large pleomorphic tumor cells ('hallmark cells'), and this feature enhances their recognition. Patient and methods We report the first case of primary brain CD30+ ALK-1+ ALCL with a T-cell phenotype, showing the combination of both the 'lymphohistiocytic' and the 'small cell' variants of the disease. A few elements consistent with 'hallmark cells' were recognizable. However, these cells were never prominent, increasing diagnostic difficulties. Immunohistochemistry results were critical for the correct interpretation. Our findings also differ from the majority of PCNSL ALCLs for the absence of tumor necrosis and the lack of prominent mitotic activity. The neuroimaging picture was not specific. A comparison with literature data concerning the clinical/instrumental features shows a very frequent meningeal involvement in PCNSL ALCLs, in contrast to the majority of PCNSLs. CONCLUSION: The occurrence of such a rare form of ALCL may widen the spectrum of differential diagnoses in PCNSL and their recognition may allow a rapid diagnosis, thus encouraging adequate treatment, which should take into account the high rate of meningeal involvement observed in these cases.

Three-dimensional time-of-flight MR angiography in the evaluation of intracranial aneurysms treated with Guglielmi detachable coils.

BACKGROUND AND PURPOSE: Intravascular treatment of intracranial aneurysms is a relatively new therapeutic technique and long-term controlled angiographic trials are needed to assess persistence of aneurysm occlusion. Our purpose was to evaluate the effectiveness of 3D time-of-flight (3D-TOF) MR angiography as a noninvasive screening tool in the follow-up of cerebral aneurysms treated with Guglielmi detachable coils (GDCs). METHODS: Forty-nine patients with 50 intracranial aneurysms previously treated with GDCs were studied with both DSA and 3D-TOF MR angiography. In 14 cases, a second follow-up examination was performed, for a total of 64 aneurysms evaluated. In 25 aneurysms, both pre- and postcontrast MR angiographic studies were obtained. RESULTS: In seven of 64 aneurysms, the MR angiographic studies were considered to be unreliable owing to the presence of artifacts that obscured part of the parent artery and did not allow an accurate evaluation of the aneurysm neck. These seven aneurysms, however, all were shown to be completely occluded at digital subtraction angiography (DSA). In the remaining 57 aneurysms, DSA revealed complete occlusion in 39 and the presence of residual patency in 18, whereas MR angiography showed complete occlusion in 38 and residual patency in 19. Enhanced MR angiography proved to be useful in evaluating residual patency in large and giant aneurysms and in better depicting the distal branch arteries. CONCLUSION: Although artifacts related to the presence of coils are evident on a considerable number of imaging studies, our findings indicate that MR angiography is useful in the evaluation of residual patency of cerebral aneurysms treated with GDCs and may eventually prove valuable in the follow-up of those cases in which a good initial correlation with DSA was demonstrated.

Intracranial vascular malformations.

Many efforts and much research have been dedicated to the field of non-invasive angiographic techniques in the past few years. Thanks first to magnetic resonance angiography (MRA) and subsequently to computed tomographic angiography (CTA), very interesting results have been obtained in the diagnosis of cerebrovascular diseases. Neck vessels are most successfully evaluated by both MRA and CTA, and the need for digital subtraction angiography (DSA) examinations in patients at risk for vascular occlusions has significantly decreased. The role and the diagnostic accuracy of these non-invasive modalities in intracranial vascular pathology is still under investigation, and several studies have been and are being performed. Both techniques have a better spatial resolution and sensitivity in detecting cerebrovascular malformations than DSA. In the diagnosis of cerebral aneurysms, both MRA and CTA - due to their high sensitivity - have become screening techniques in the population at risk for subarachnoid hemorrhage, these techniques may become basic diagnostic modalities in treatment planning. The results are less satisfying in the evaluation of brain arteriovenous malformations and in the different steps of pre- and post-therapeutic evaluation.

Acute subarachnoid haemorrhage: 3D time-of-flight MR angiography versus intra-arterial digital angiography.

To evaluate the efficacy and reliability of 3D time-of-flight MR angiography (TOF MRA) as a noninvasive procedure, 27 patients with acute subarachnoid haemorrhage (SAH) were studied with MRA immediately before or after intra-arterial digital subtraction angiography (DSA).3DTOF MRA was performed with an axial slab of 60 mm centered on the circle of Willis and isotropic voxels. DSA showed 22 aneurysms and 1 dural arteriovenous fistula in 21 patients; the aneurysms ranged in size from 2 to 8mm. MRA failed to show 2 small aneurysms, at the origin of the posterior and anterior communicating arteries. The 3D display of the intracranial vessels obtained with maximum intensity projection (MIP) or targetted MIP sometimes rendered the aneurysms better than DSA. However, due to its high spatial resolution, DSA more clearly defined the overall anatomy of the walls of the normal and abnormal vessels.

Three dimensional time-of-flight magnetic resonance angiography in carotid artery surgery: a comparison with digital subtraction angiography.

Three dimensional time-of-flight magnetic resonance angiography (MRA) and intra-arterial digital subtraction angiography (DSA), considered the gold-standard technique, were compared for pre- and postoperative evaluation of the carotid bifurcation. Images of suitable quality of 194 bifurcations were available with both techniques. Percentage stenosis was graded into 5 groups: A = 0-29%, B = 30-59%, C = 60-89%, D = 90-99%, E = 100% (occlusion). Preoperative MRA (126 bifurcations) overgraded the stenosis in 14 cases and undergraded it in 11. The two techniques agreed in 101 cases and the extent of misgrading was never more than one category. Regression analysis showed a good correlation between the two methods. Severe ulceration was better identified by DSA. As far as the surgical indication was concerned, MRA had a sensitivity of 92.6% and a specificity of 98.3%. In 68 operated cases, postoperative MRA and intraoperative completion angiography showed a satisfactory endarterectomy with no residual stenosis in any of the cases. In conclusion, MRA seems an accurate modality for imaging of carotid bifurcations. Significant limitations still exist for an adequate demonstration of intracranial circulation.

Are sensorimotor strokes lacunar strokes? A case-control study of lacunar and non-lacunar infarcts.

To determine whether sensorimotor strokes should be considered as lacunar syndromes 34 consecutive patients with first-ever ischaemic sensorimotor stroke were evaluated and compared with 103 patients with non-lacunar infarcts and another 88 patients with lacunar infarcts. Potential thromboembolic sources were more frequent in patients with non-lacunar infarcts (p = 0.003, versus sensorimotor strokes). Although the overall prevalence of hypodense lesions at CT scan was not significantly different among the three groups, lacunar lesions were found in 47.1% of sensorimotor strokes, compared with 6.8% of non-lacunar infarcts (p less than 0.0001). In a mean follow up period of 28.7 months, the incidence of stroke and myocardial infarction among sensorimotor strokes was similar to that of patients with lacunar infarct, but significantly lower than in non-lacunar infarcts (p less than 0.05). These results demonstrate important differences between sensorimotor and non-lacunar infarcts, but quite similar findings in sensorimotor and lacunar strokes, and thus support the theory that sensorimotor strokes are commonly due to lacunar lesions.

Analysis of diagnostic procedure costs for cerebrovascular disease admission to a highly specialized hospital.

Length of stay and hospital costs for cerebrovascular disease admissions depend on several hospital-, patient- and disease-related factors. To determine the incidence of each of these factors we studied 240 admissions for cerebrovascular diseases in a neurology division and in two medical divisions of a highly specialized hospital. Statistical analysis of the data collected from the case records revealed the effect of several factors. Some increased only the length of stay (severe neurological sequels on discharge; stay in general medicine, diagnosis of hemorrhage, arterial hypertension). Others increased investigation costs (length of stay, marital status), and costs were higher in a specialists ward. Length of stay was shorter where the nurse/bed ratio was higher. Old age and male sex were associated with a lower cost of diagnostic procedures.