Whole-body [18F]-FDG-PET/MRI for staging of pediatric non-Hodgkin lymphoma: first results from a single-center evaluation.

AIM: In 2015, the revised International Pediatric Non-Hodgkin Lymphoma Staging System was published. It mentions [18F]-FDG-PET/MRI as the latest method to perform whole-body imaging. However, supporting data are pending. Our aim was to investigate the performance of whole-body [18F]-FDG-PET/MRI in pediatric non-Hodgkin lymphoma patients by using a limited number of MRI sequences. MATERIALS AND METHODS: Ten pediatric patients with histologically proven non-Hodgkin lymphoma underwent whole-body [18F]-FDG-PET/MRI at staging. The retrospective analysis included three steps: First, [18F]-FDG-PET and MR scans were evaluated separately by a nuclear medicine physician and a pediatric radiologist. Nineteen nodal and two extranodal regions as well as six organs were checked for involvement. Second, discrepant findings were reviewed together in order to reach consensus. Third, [18F]-FDG-PET/MRI findings were correlated with the results of other clinical investigations. RESULTS: Of the 190 lymph node regions evaluated, four were rated controversial. Consensus was reached by considering metabolic, functional and morphologic information combined. Concordantly, [18F]-FDG-PET and MRI detected Waldeyer's ring involvement in two patients whose Waldeyer's ring was negative on clinical assessment. In four patients MRI showed pleural effusion. However, in only two of them an increased glucose metabolism as a reliable sign of pleural involvement was detectable. In six patients [18F]-FDG-PET and MRI detected skeletal lesions although bone marrow biopsy was positive in only one of them. CONCLUSION: Despite the small number of cases evaluated, whole-body [18F]-FDG-PET turned out to be a valuable tool for staging of pediatric non-Hodgkin lymphoma.

Mutations in the Nijmegen Breakage Syndrome gene (NBS1) in childhood acute lymphoblastic leukemia (ALL).

The Nijmegen Breakage Syndrome (NBS) is a rare autosomal recessive disorder associated with immune deficiency, chromosome fragility, and increased susceptibility to lymphoid malignancies. The aim of the present study was to elucidate the potential role of the gene mutated in NBS (NBS1) in the pathogenesis and disease progression of childhood acute lymphoblastic leukemia (ALL). Samples from 47 children with first relapse of ALL were analyzed for mutations in all 16 exons of the NBS1 gene, and in 7 of them (14.9%), four novel amino acid substitutions were identified. Mutations S93L, D95N, and I171V occur in the two known domains of nibrin that are probably involved in protein-protein interactions. Germ-line origin of the I171V mutation was confirmed in three patients, whereas the D95N exchange was present only in leukemic cells. The R215W mutation was observed in one ALL but also in a population-based study and probably represents a rare sequence variant. No additional mutations were found on the second allele in any of these seven patients. The observed NBS1 gene mutations in ALL patients points to its possible involvement in the pathogenesis of this disease.

Activation of the HIF pathway in childhood ALL, prognostic implications of VEGF.

Hypoxia-inducible factor 1 (HIF-1) controls angiogenesis and glycolysis, two leading characteristics of solid tumor invasion, metastasis, and lethality. Increased angiogenesis is also found in the bone marrow (BM) of leukemias. Less is known in leukemia about the role of HIF-1 and vascular endothelial growth factor (VEGF), the most important proangiogenic target gene of HIF-1. We show by immunohistochemistry that the oxygen-regulated component of HIF-1 (HIF-1alpha) is overexpressed in clusters of leukemic cells in BM specimens of childhood acute lymphoblastic leukemia (ALL) and absent in biopsies of normal BM. Half the HIF-1alpha-positive ALL biopsies exhibited VEGF coexpression. Among 96 children with relapsed ALL, diagnostic BM aspirates with high VEGF mRNA levels were associated with a significantly lower probability of event-free survival at 3 years (0.31+/-0.08 vs 0.65+/-0.07, P=0.003). Those with poor molecular response to therapy (evaluated by MRD assessment) had 2.2-fold higher VEGF levels than those responding well to chemotherapy (P=0.005). In conclusion, the data demonstrate activation of the HIF pathway in the BM of ALL patients and indicate that the expression of HIF target genes, such as VEGF, play an important role in leukemia progression, therapy response, and outcome.

Absence of mutations in the CDKN2 binding site of CDK4 in childhood acute lymphoblastic leukemia.

The cell cycle regulatory circuit resulting in phosphorylation of the retinoblastoma protein (pRB) is frequently altered in human cancers. Several mechanisms of disruption are known in that pathway. In childhood acute lymphoblastic leukemia (ALL), the main disrupting mechanism is the homozygous deletion of the CDKN2 (cyclin dependent kinase inhibitor 2) genes: p16CDKN2a, p15CDKN2b, and p19ARF. Another pRB pathway disturbance is a previously described point mutation in the exon 2 of CDK4, a pRB phosphorylating enzyme, which abrogates binding of the latter to its inhibitors, p16CDKN2a and p15CDKN2b. Here we report the absence of point mutations in the CDKN2-binding site of CDK4 in 100 cases of childhood ALL, 2 cases of childhood chronic myeloid leukemia and 9 hematologic cell lines screened by PCR-SSCP (polymerase chain reaction single stranded conformational polymorphism gel electrophoresis), thereby minimizing the possibility of the existence of these specific CDK4 mutations in childhood ALL.

Nuclear magnetic resonance imaging of brain tumors unrevealed by CT.

The important contributions of nuclear magnetic resonance (NMR) in the diagnosis of brain tumours are demonstrated in this report. In 2 patients, one with a completely normal and the other with a slightly abnormal CT, prominent lesions were detected by NMR and histologically confirmed as astrocytomas.

Magnetic resonance imaging of spinal cord syndromes.

Thirty-four patients with intramedullary space-occupying lesions or cord compression syndromes were examined with a resistive and two different superconductive magnetic resonance (MR) imaging units. Studies were done primarily by the spin-echo (SE) technique and in the majority of patients different pulse sequences were used. Images with short echo-time (TE) and short recovery-time (TR) were best for demonstration of spinal cord anatomy, for depicting cystic portions in intramedullary tumours and for showing syringomyelia. Solid intramedullary tumours showed normal cord signal intensity. Images with prolonged TE and TR predominantly enhanced CSF signal intensity and, to a more considerable extent, solid intramedullary tumours. Thus, the diameter of the subarachnoid space and the presence of a solid intramedullary tumour, not concomitant with a significant enlargement of the spinal cord, could only be recognized on these prolonged SE images. Major advantages of MR in comparison to CT are that the spinal cord can be imaged in the sagittal plane and that beam hardening artifacts do not occur; in comparison to myelography the cord can be imaged directly by MR. Partial volume is a major limitation of MR, not only in the preferably applied sagittal plane. The choice of slice thickness adequate to the diameter of the lesion and straight positioning of the patient for sagittal single slice midline images are fundamental for reliable MR investigations. Another limitation to MR is that cortical bone gives no signal. The actual diameter of the spinal canal therefore cannot be correctly appreciated and consequently it was difficult or impossible to assess spinal stenosis.

[Magnetic resonance tomography (MRT) in the diagnosis of Failed Back Surgery Syndrome (FBSS)]. / Die Magnetresonanztomographie (MRT) in der Diagnostik des Failed Back Surgery Syndroms (FBSS).

MRT was performed, using a 0.5 and 1.5 Tesla magnet, on 150 patients with FBSS between three days and 23 years following lumbar disc surgery. T1-weighted spin echo sequences were obtained before and after the application of gadolinium (0.15 mmol/kg). In 67 patients the MRT findings were compared with surgical observations. MRT had a sensitivity of 94% in diagnosing recurrent prolapse, a specificity of 100% and accuracy of 94%. The ventral epidural scar tissue, the disc and the neighbouring vertebral bodies showed increased contrast uptake over a prolonged post-operative period.

[MR and CT patterns of neurocysticercosis]. / MR- und CT-Muster der Neurozystizerkose.

MRI and CT manifestations were studied in five cases of neurocysticercosis. As demonstrated by long-term follow-ups the disease usually causes multiple lesions the morphology of which depends on the life cycle of the parasite. Tissue lesions consist of three main types: 1) vital cysticerci, 2) inflammatory parenchymatous reactions following degenerating cysts and 3) calcified granulomas. MRI provides all information that is given by CT except for small calcifications which are usually missed. Morphological details of vital cysticerci like cyst wall and scolex are better outlined by MRI. When i.v. contrast medium is applied, it leads to nodular or annular enhancement of inflamed tissue. The sensitivity of MRI towards edema caused by parasite exceeds that of CT by several weeks. CT and MRI are complementary methods providing at the present time the highest degree of specificity in diagnosing neurocysticercosis.

DWI in transient global amnesia and TIA: proposal for an ischaemic origin of TGA.

There are conflicting reports concerning signal intensity changes in transient global amnesia (TGA) using diffusion weighted imaging (DWI). We prospectively analysed DWI signal intensity changes in TIA and TGA patients, and compared the clinical characteristics and risk factors of both groups. Using DWI and conventional T1 and T2 weighted turbo spin echo sequences, 28 patients with acute TGA (13 men, mean age 61.5 years) and 74 TIA patients (47 men, mean age 62.4 years) were studied within 48 hours after symptom onset. Every patient underwent an intensive diagnostic investigation. In 10/28 (36%) of the TGA patients and 21/74 (28%) of the TIA patients, DWI signal intensity changes occurred. The time to DWI and the duration of symptoms were comparable in TIA and TGA patients. Overall, TIA patients showed an increased prevalence of vascular risk factors compared with TGA patients. In the TGA group, patients with abnormal DWI showed carotid atherosclerosis significantly more frequently. Based on our data, we suggest that the aetiology of TGA could be explained by an ischaemic event; due to arterial thrombembolic ischaemia in one subgroup, particularly in those patients with increased vascular risk factors, and due to venous ischaemia in another subgroup with valsalva-like activities before symptom onset.

Polarization-dependent photothermal beam deflection for the determination of the order parameter C(2) in a laser-oriented polymer system.

We demonstrate polarization-dependent photothermal beam deflection as a powerful tool for analyzing quasi-two-dimensional molecular orientation. As examples we used two laser-beam-oriented polymer systems: DR1 in poly(methyl methacrylate) (PMMA) and PMMA with covalently bound DR1 and for comparison Phenol Blue in PMMA. Different order parameters C(2), for these systems have been found. It was also possible to orient by laser beam the DR1 chromophores cyclically by changing the polarization direction of the orienting laser beam and following these chromophore reorientations. The long-term stability of the orientation was investigated as well. The irreversible bleaching that is due to this laser treatment could be determined. Angular hole burning could easily be detected in these systems.

[The significance of leukoaraiosis. A current evaluation and differential diagnosis]. / Bedeutung der Leukoaraiosis. Eine Bestandsaufnahme und differentialdiagnostische Abgrenzung.

Bilateral symmetric changes in the cerebral hemispheric white matter are found with increasing frequency using CT and MRI techniques. These unspecific changes of the white matter signal are often called leukoaraiosis. They differ from the normal white matter signal. These changes are found with increasing frequency in persons older than 60 years and also patients with dementia and cerebrovascular diseases. The pathogenesis, clinical significance and morphological substrate are unclear. The aim of this review is to summarise the actual knowledge about the etiology and clinical signs and symptoms found in patients with leukoaraiosis. This term should not be used when white matter changes are found in patients younger than 35 years, with an unilateral onset, asymmetric distribution, and extensive changes all over the infra- and supratentorial white matter area. Neuroradiological and clinical criteria are given to differentiate between leukoaraiosis and diseases of the white matter, especially enlarged Virchow-Robin spaces, lacunar infarction, subcortical arteriosclerotic angiopathy (Binswanger's disease), leukoencephalopathy of different origin, and demyelinating diseases.

Magnetic resonance ventriculography with gadolinium DTPA: report of two cases.

We report intrathecal use of gadolinium DTPA for MRI of the cerebrospinal fluid (CSF). In two patients with leptomeningeal carcinomatosis, we injected 0.01 mmol gadolinium DTPA into the lateral ventricle via an Ommaya device. Coronal T1-weighted images of the head were obtained at 0.2 T prior to and after injection. There was pronounced enhancement of CSF close to the injection site, allowing good delineation of CSF and surrounding brain tissue. No side effects occurred. MRI with intrathecal administration of highly diluted gadolinium DTPA may be a promising alternative to conventional investigation of CSF-filled cavities using iodinated X-ray contrast media or radionuclides.

Correlation between quantitative EMG and muscle MRI in patients with axonal neuropathy.

The aim of the study was to investigate whether there are correlations between electromyography (EMG) data and findings in muscle magnetic resonance imaging (MRI). Quantitative EMG data and the amount of pathologic spontaneous activity (PSA) were compared with MRI signal intensities of the tibialis anterior muscles of 20 patients with axonal polyneuropathy and 14 healthy subjects. Using hierarchical regression analysis, the mean motor unit action potential (MUAP) size index (SI) and the amount of PSA were accurate predictors of T1-weighted signal intensity in MRI, an expression of fatty degeneration. The MUAP SI was superior to MUAP amplitude in explaining the variance of T1 signal intensity. Age was not a relevant factor. A high correlation was found between the amount of PSA and the T2-weighted signal intensity in short tau inversion recovery sequence. Magnetic resonance imaging demonstrates the structural changes and thus visualizes the outcome of the functional changes of denervation and reinnervation detected by EMG.

[Circumscribed vasculitis with posterior infarct in Hashimoto encephalopathy]. / Umschriebene Vaskulitis mit Posteriorinfarkt bei Hashimoto-Enzephalopathie.

The aetiology of Hashimoto's encephalopathy is still unknown. A 52-year-old woman with so far unspecific thyroid disorder presented with acute onset of right-sided sensory loss and visual disturbances. The neurological examination revealed a right upper quadrant anopsia and subtle right-sided sensory loss and weakness. The cranial MRI showed a left-sided cerebral infarction. MR angiography demonstrated a stenosis of the proximal segment of the left posterior cerebral artery, which was confirmed by conventional catheter angiography. The patient had no cardiovascular risk factors, no signs of systemic vasculitis, and no thromboembolic disorder. Thyroid function tests showed a subclinical hypothyroidism with plasma TSH level of 12.0 mU/ml, and thyroid antibodies were markedly elevated (hTG-AB 3390 U/ml, TPO-AB > 8000 U/ml). Typical features of Hashimoto's disease were demonstrated by ultrasound and scintigraphic examination of the thyroid gland. To the best of our knowledge, this is the first description of Hashimoto encephalopathy with localised vasculitis of the posterior cerebral arteries and left posterior infarction. It could be shown that the MR angiogram is a feasible tool to demonstrate regression of the vasculitis under glucocorticoid therapy.