Retinoblastoma and optic nerve enhancement on MRI: not always extraocular tumour extension.
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Child, Preschool↗
Biomedical subjects
J A Castelijns
Publications and source records attributed to J A Castelijns.
Classification of multiple sclerosis patients by latent class analysis of magnetic resonance imaging characteristics.
BACKGROUND: Disease heterogeneity is a major issue in multiple sclerosis (MS). Classification of MS patients is usually based on clinical characteristics. More recently, a pathological classification has been presented. While clinical subtypes differ by magnetic resonance imaging (MRI) signature on a group level, a classification of individual MS patients based purely on MRI characteristics has not been presented so far. OBJECTIVES: To investigate whether a restricted classification of MS patients can be made based on a combination of quantitative and qualitative MRI characteristics and to test whether the resulting subgroups are associated with clinical and laboratory characteristics. METHODS: MRI examinations of the brain and spinal cord of 50 patients were scored for 21 quantitative and qualitative characteristics. Using latent class analysis, subgroups were identified, for whom disease characteristics and laboratory measures were compared. RESULTS: Latent class analysis revealed two subgroups that mainly differed in the extent of lesion confluency and MRI correlates of neuronal loss in the brain. Demographics and disease characteristics were comparable except for cognitive deficits. No correlations with laboratory measures were found. CONCLUSIONS: Latent class analysis offers a feasible approach for classifying subgroups of MS patients based on the presence of MRI characteristics. The reproducibility, longitudinal evolution and further clinical or prognostic relevance of the observed classification will have to be explored in a larger and independent sample of patients.
Adult↗
Normal-appearing white matter changes vary with distance to lesions in multiple sclerosis.
BACKGROUND AND PURPOSE: Multiple sclerosis (MS) disease processes in normal-appearing white matter (NAWM) may be different close to MR-visible lesions than farther from these lesions. We aimed to investigate the relationship of NAWM changes to the distance to the lesions. METHODS: We measured B(1)-corrected T1 and magnetization transfer ratio (MTR) maps in 63 patients with MS (11 primary progressive, 34 relapsing-remitting, 18 secondary progressive). We used histogram analyses to assess the global properties of lesions, of 4 consecutive 1-mm pixel layers of NAWM around the lesions, and of distant NAWM located at least 4-mm from lesions in all directions. In 22 healthy controls, we measured white matter MTR and T1 histograms. Histogram parameters were statistically analyzed by using a linear mixed model. RESULTS: The first and second NAWM pixel layers around the lesions had a significantly lower MTR histogram peak position than distant NAWM, whereas T1 histogram peak position was similar between all types of NAWM. Furthermore, MTR histograms of distant NAWM were statistically indistinguishable from those of control white matter, whereas T1 histograms of distant NAWM had significantly decreased peak height for relapsing-remitting MS and secondary progressive MS and significantly increased peak position for secondary progressive MS. CONCLUSION: Our results may suggest that axonal damage and demyelination in NAWM mainly arise as a secondary result of visible lesions, with the largest effect close to these lesions. NAWM disease farther from the lesions may be mainly characterized by subtle blood-brain barrier damage, with leakage of fibrinogen into the parenchyma and microplaque formation, processes that are detected with T1 but not with MTR.
Adult↗
Patterns of enhancing lesion evolution in multiple sclerosis are uniform within patients.
BACKGROUND: Histopathologic studies suggest that lesion development differs between patients with multiple sclerosis (MS), but that all lesions appear similar within patients. It is unclear whether the same applies to the evolution of lesions on T1-weighted MRI. OBJECTIVE: To evaluate lesion evolution on MRI, comparing variance within and between patients, as well as the relationship between MRI lesion development and clinical characteristics. METHODS: In 48 patients, signal intensity at baseline and at follow-up on T1-weighted MRI of 789 newly enhancing lesions was studied in relationship with clinical data. Patients were included on the basis of showing at least five enhancing lesions that could be followed on monthly scans for 6 months. Variance component analysis and multilevel analysis were used to compare within-patient and between-patient variability. RESULTS: Although various types of lesion evolution could be observed within a single patient, between-patient variance was considerably larger than within-patient variance for MRI parameters used to describe lesion evolution, indicating that lesion evolution is a patient-specific phenomenon. Evolution of lesions in patients with secondary progressive disease more frequently followed a hypointense-hypointense pattern than in patients with relapsing-remitting disease (odds ratio 4.2). Patients with a benign disease course had more persistent isointense lesions at follow-up, whereas patients with aggressive disease had more hypointense lesions. CONCLUSION: Lesion evolution on MRI appears to be a patient-specific phenomenon, although the outcome seems to vary according to the phase and severity of the disease.
Central Nervous System↗
MR spectroscopic evidence for glial increase but not for neuro-axonal damage in MS normal-appearing white matter.
Quantitative single-voxel, short echo-time (TE) MR spectroscopy (MRS) was used to determine metabolite concentrations in the cerebral normal-appearing white matter (NAWM) of 76 patients with multiple sclerosis (MS), and the WM of 25 controls. In NAWM of all MS disease types (primary progressive, relapsing-remitting, and secondary progressive), the concentration ratio of total N-acetyl-aspartate (tNAA)/total creatine (tCr) was decreased compared to controls. Remarkably, this was entirely due to an increase of tCr in MS patients, whereas there was no difference in tNAA. Separate quantification of the two tNAA components yielded no significant difference in NAA (N-acetyl-aspartate), while the concentration of NAAG (N-acetyl-aspartyl-glutamate) was slightly-but significantly-elevated in MS patients. Myo-inositol (Ins) was strongly increased in MS patients, and choline-containing compounds (Cho) were mildly increased. There were no metabolite differences between disease types, and no correlations with disability scores. The results are supported by measures of spectral quality, which were identical for patients and controls. In conclusion, MS NAWM containing very little perilesional tissue is characterized by increased glial cell numbers (increase of Ins and tCr) without evidence of axonal dysfunction (normal NAA). Further studies should elucidate the mechanism underlying increased NAAG in MS NAWM.
Adolescent↗
Screening for distant metastases in patients with head and neck cancer: what is the current clinical practice?
OBJECTIVES: The detection of distant metastases during screening influences the choice of treatment in patients with head and neck squamous cell carcinoma (HNSCC). There is no consensus on the diagnostic technique that has to be used nor on the subgroup of HNSCC patients that may benefit from screening. DESIGN: Questionnaire on current practice concerning the diagnostic work-up in HNSCC patients for screening for distant metastases. PARTICIPANTS: Investigators in the 12 otolaryngology / head and neck and seven oromaxillofacial departments treating head and neck cancer in the Netherlands. RESULTS: The response rate was 100%. Indications for screening were cervical lymph node metastases (63%), mutilating surgery (58%), locoregional recurrence (47%), advanced T-stage (32%), second primary tumour (21%). Diagnostic techniques routinely used for screening besides chest X-ray were chest CT (84%), liver ultrasound (53%), liver CT (16%) and bone scintigraphy (42%). Forty-two per cent of the clinicians were not satisfied with the current methods of screening. CONCLUSION: This survey shows a substantial variation in indications and diagnostic techniques used for screening for distant metastases between the major institutions treating head and neck cancer in the Netherlands. There is a need for guidelines for screening for distant metastases in patients with head and neck cancer.
Bone and Bones↗
Spinal cord abnormalities in recently diagnosed MS patients: added value of spinal MRI examination.
OBJECTIVE: The most recent diagnostic criteria for multiple sclerosis (MS) ascertain that findings from spinal cord MRI can be used to demonstrate dissemination in space. Because little is known about the prevalence and characteristics of cord lesions early in the disease, the authors studied the prevalence of spinal cord abnormalities in patients with early-stage MS and assessed their impact on diagnostic classification. METHODS: The brains and spinal cords of 104 recently diagnosed patients with MS were examined. Median interval between first symptom and diagnosis was 18.4 months. The brain MRI protocol included before and after gadolinium axial T1-weighted conventional spin-echo sequences and dual-echo spin-echo images. For spinal cord MRI, sagittal cardiac-triggered dual-echo T2-weighted and sagittal T1-weighted spin-echo images were included. Clinical assessment for each patient included age, sex, clinical signs for spinal cord involvement, and Expanded Disability Status Scale. RESULTS: Abnormal cord MRIs were found in 83% of patients, usually with only focal lesions. Diffuse cord abnormalities were found in 13% of patients, although in isolation they were found in only three patients. Focal cord lesions were often multiple (median number, 3.0), small (median, 0.8 vertebral segments), and primarily (56.4%) situated in the cervical spinal cord. In 68 of 104 patients (65.4%), two or more focal lesions were visible on spinal cord images. The criteria for dissemination in space, as defined in the McDonald criteria for the brain, were met in only 66.3% of the patients. This percentage increased to 84.6% when spinal cord MRI abnormalities were also included. CONCLUSION: Spinal cord abnormalities are prevalent in patients with early-stage MS, have distinct morphologic characteristics, and help to determine dissemination in space at time of diagnosis.
Adult↗
Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study.
PURPOSE: To determine the safety profile and activity of the combination of docetaxel, cisplatin and 5-fluorouracil (5-FU) in chemotherapy-naive patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with locally advanced unresectable SCCHN were treated with docetaxel and cisplatin both as a 1-h infusion on day 1 followed by a continuous infusion of 5-FU for 5 days. Cycles were planned every 3 weeks up to four cycles, whereafter the patients were treated with locoregional radiotherapy. Two dose levels were studied. Doses in level I were 75 mg/m(2) of docetaxel, 75 mg/m(2) of cisplatin and 750 mg/m(2)/day of 5-FU; in level II the cisplatin dose was escalated to 100 mg/m(2). Following chemotherapy, all patients were to receive curative radiotherapy according to the standards in the different institutions. RESULTS: Twenty-five patients were treated at dose level I with 86 cycles (median four; range one to four), and 23 at dose level II with 84 cycles (median four; range two to four). The median relative dose intensity was 0.99 (range 0.86-1.04) at level I and 0.94 (range 0.79-1.02) at level II. The response rate in the intention-to-treat population was 64% [95% confidence interval (CI) 42.5% to 82%] in level I and 78.3% (95% CI 56.3% to 92.5%) in level II; all were partial responses. The maximum tolerated dose was reached at level II with renal toxicity, nausea, stomatitis and thrombocytopenia as principal dose-limiting toxicities. The median survival of the 48 patients was 18.5 months. The survival at 12, 18, 24 and 30 months was 69, 54, 41 and 31%, respectively. CONCLUSIONS: The combination of docetaxel, cisplatin and 5-FU associated with prophylactic ciprofloxacin is feasible and active in patients with SCCHN. Dose level I is recommended for phase III testing.
Adult↗
Interobserver variability in the radiological assessment of response to chemotherapy in glioma.
OBJECTIVE: To assess the interobserver variability in the radiologic assessment of response to chemotherapy in patients with recurrent glioma. METHODS: Five clinicians with experience in the treatment and follow-up of patients with glioma measured tumor size in 20 pairs of CT and 20 pairs of MRI scans of 35 patients who had been treated with chemotherapy for recurrent glioma. Tumor size was defined as the product of the two largest perpendicular enhancing tumor diameters on the postcontrast images. To assess the interobserver variability in the measurements of tumor size, and in the classification according to the widely used Macdonald response criteria, intraclass correlation coefficients (ICC) and weighted kappa values were calculated. RESULTS: Substantial interobserver agreement was noted in the manual, two-dimensional measurements of tumor size on CT and MRI in patients treated with chemotherapy for recurrent glioma (overall ICC 0.64). Classification of response to chemotherapy according to the Macdonald criteria resulted in moderate interobserver agreement (overall weighted kappa 0.51). In 65% of evaluated CT and in 55% of evaluated MRI studies, no complete consensus was found for the categorical tumor response measurement. CONCLUSION: The radiologic assessment of response to chemotherapy in patients with recurrent glioma is susceptible to considerable interobserver variability. This underlines the difficulties that arise in scoring response to chemotherapy by conventional radiologic techniques.
Adult↗
Lymphoscintigraphic details of sentinel lymph node detection in 82 patients with squamous cell carcinoma of the oral cavity and oropharynx.
Lymphoscintigraphy for sentinel node (SN) detection has been studied extensively in melanoma and breast cancer. In head and neck squamous cell carcinoma (HNSCC), however, experience in this field is relatively meagre. The purpose of this study was to document and evaluate lymphoscintigraphic findings in HNSCC patients. Eighty-two patients with clinical T1-T4 N0 SCC of the oral cavity or oropharynx received peritumoral injections of 25-75 MBq 99mTc-colloidal albumin (CA). Dynamic lymphoscintigraphy was performed in lateral projection for 20 min, followed by 2 min static imaging in anterior projection. In 26 patients, additional static images were obtained 2-6 h after injection of the tracer. In four of 82 patients, both early and late imaging revealed no tracer transport. In 78 of 82 patients, one (60), two (14) or three (4) SNs could be visualized, either by dynamic scintigraphy (73) or delayed static imaging (5). In 48 of 78 (62%) patients, the SN was visualized within the first minute of dynamic imaging. In particular, SNs of tumours of the mobile tongue were visualized within the first minute. No effect of T-stage or 99mTc-CA dose on the transport time of the tracer towards the SN was seen. The distribution of the SNs in the various levels of the neck relative to the primary tumour sites within the oral cavity was in concordance with the patterns of lymph node metastases reported traditionally for patients with SCC in the oral cavity. This study demonstrates the different variables affecting SN identification with lymphoscintigraphy using 99mTc-CA in HNSCC patients.
Adult↗
Axonal damage in the spinal cord of MS patients occurs largely independent of T2 MRI lesions.
OBJECTIVE: To determine the degree of axonal damage in relationship to signal abnormalities on T2-weighted high-resolution MRI in spinal cord tissue of patients with MS. METHODS: Spinal cord specimens of nine patients with MS and four controls were imaged at high resolution (4.7 T) in an axial plane and scored for lesions with increased signal intensity (SI). Histopathologic sections were cut and immunostained with NE14 (neurofilament marker) and Luxol fast blue (myelin stain). For each area, axonal density and diameter were quantified; axonal irregularity, NE14 axonal staining intensity, and myelin content were semiquantitatively scored. Included were 209 areas from MS cases and 109 areas from control cases distributed over lateral, posterior, and anterior columns. RESULTS: In control cases, no SI changes were found, average density of axons was 26,989/mm(2), average diameter was 1.1 micro m, and all scores for axonal irregularity, NE14 staining intensity, and myelin were normal. In MS cases, areas with increased SI were found, average axonal density was 11,807/mm(2) (p < 0.0001), and average axonal diameter 2.0 micro m (p = 0.001). Areas with high SI on MRI had lowest axonal density (average count: 10,504/mm(2); range: 3,433 to 26,325/mm(2)), largest diameter (average: 2.3 micro m; range: 1.0 to 4.0 micro m), and highest axonal irregularity and NE14 staining intensity compared to normal appearing cord tissue (NACT). However, NACT of MS cases also had lower axonal density (14,158/mm(2)) and higher average axonal diameter (1.6 micro m) than controls. CONCLUSIONS: Marked axonal loss occurs in MS spinal cords, largely independent of the degree of signal abnormality on T2-weighted MRI.
Adult↗
Optimizing the association between disability and biological markers in MS.
OBJECTIVE: Axonal damage is an important feature of MS pathology and the likely substrate of development of progressive disability. Brain volume measurement on MRI can be used as an overall marker of tissue damage and axonal loss. The authors studied the relation of brain volume measurements with the MS Functional Composite (MSFC) in an attempt to improve the clinico-radiologic association. METHODS: In 137 patients with MS (80 relapsing-remitting [RR], 36 secondary progressive [SP], and 21 primary progressive [PP]) and 12 healthy controls, a brain MRI scan was obtained. Patients also underwent MSFC and Expanded Disability Status Scale (EDSS) assessments. MRI analysis included determination of hypointense T1- and hyperintense T2-weighted lesion load, and two brain volume measurements: 1) the parenchymal fraction (PF): whole brain parenchyma/intracranial volume; and 2) the ventricular fraction (VF): ventricular volume/whole brain parenchyma. RESULTS: The median PF was smaller and the median VF larger in the patient group (0.81 for PF and 0.029 for VF) than in the control group (0.87 for PF, p < 0.001; and 0.013 for VF, p < 0.01). For the patient population, moderate correlations were found between brain volume measurements and MSFC (0.36 for PF and -0.40 for VF). Patients with short disease duration showed a correlation of MSFC with both brain and lesion volume measurements on MRI, whereas patients with long disease duration only showed a correlation with brain volume measurements. CONCLUSION: Brain volume measurements are correlated with disability as assessed by the MSFC. Although in the early phase of the disease the amount of focal demyelination is important, the residual brain volume seems to be more relevant in determining disability in later phases of the disease.
Adolescent↗
Hypointense lesions on T1-weighted spin-echo magnetic resonance imaging: relation to clinical characteristics in subgroups of patients with multiple sclerosis.
CONTEXT: Hypointense lesions on T1-weighted spin-echo magnetic resonance images (T1 lesions) represent destructive multiple sclerosis (MS) lesions, consisting of axonal loss and matrix destruction. These lesions are being used as a secondary outcome measure in phase III clinical trials. Clinical determinants of T1 lesions may differ between subgroups of patients with MS and subsequently may have implications for the selection of patients for clinical trials. OBJECTIVE: To determine if clinical characteristics of patients with MS are related to T1 lesion volume. DESIGN: A survey of 138 patients with MS (52 with relapsing-remitting MS, 44 with secondary progressive MS, and 42 with primary progressive MS). SETTING: The Magnetic Resonance Center for Multiple Sclerosis Research, University Hospital "Vrije Universiteit," Amsterdam, the Netherlands. MAIN OUTCOME MEASURES: Type of MS, Expanded Disability Status Scale (EDSS) score, sex, age at first symptoms, and T1 lesion volume. RESULTS: Patients with secondary progressive MS have the highest T1 lesion volume. Patients with relapsing-remitting MS have a lower T1/T2 ratio than patients with secondary progressive MS and patients with primary progressive MS. In patients with relapsing-remitting MS and secondary progressive MS, T1 lesion volume relates to disease duration and EDSS score, while in patients with primary progressive MS sex is important. A trend toward higher T1 lesion volume was shown for male patients with primary progressive MS when compared with female patients with primary progressive MS (1.0 cm(3) vs 0.3 cm(3), P=.03); a trend toward higher T1 lesion volume was found with age at onset in patients with relapsing-remitting MS and in patients with primary progressive MS. CONCLUSIONS: In patients with MS different clinical characteristics associate with T1 lesion volume, suggesting a more destructive type of lesions in certain subgroups. A possible sex difference in (destructive) lesion development on magnetic resonance imaging should be evaluated in more detail, preferably in a cohort.
Adult↗
Post-mortem high-resolution MRI of the spinal cord in multiple sclerosis: a correlative study with conventional MRI, histopathology and clinical phenotype.
We used high-resolution MRI to study the post-mortem appearance of spinal cord multiple sclerosis in relation to histopathology and low-resolution images. Fifty-nine 3 cm long formalin-fixed spinal cord specimens from 19 multiple sclerosis patients and three controls were studied. Clinical characteristics of each patient were reviewed. High-field MRI consisted of proton-density weighted spin-echo imaging with an in-plane resolution of 80 microm. Specimens were also imaged at 1.0 T, with 1 mm pixel resolution. After MRI, the specimens were cut at 5 mm intervals and stained for myelin (Luxol fast blue/cresyl violet) and axons (Bodian method). Two observers scored the MRIs for abnormalities and divided them into (i) well-delineated areas of high signal intensity (SI) and (ii) poorly defined areas of mildly increased SI. Abnormalities were scored semiquantitatively, white matter and grey matter separately. In 81 sections the total area of abnormalities per section was measured on both histopathology sections and on matched high-field MRIs. Abnormalities ranged from just a few abnormal areas to complete involvement of the spinal cord specimen. Patients with an aggressive disease course had more abnormalities than patients with a mild or intermediate disease course. Areas of mildly increased SI were seen in all specimens, and were often found around focal high-SI lesions. However, in six patients, areas of mildly increased SI were the predominant finding on the MRIs, correlating with a primary progressive disease course. Histopathologically, high-SI areas correlated with complete demyelination, while mildly increased SI corresponded with partial demyelination. All areas scored as abnormal by the neuropathologist were also found on the MRIs, and sizes measured using both methods correlated well (r = 0.85, P<0.01). On conventional MRIs, abnormalities could be recognized fairly well. However, better differentiation could be made between high-SI and mildly increased SI abnormalities on the 4.7 T images. In conclusion, high-resolution MRI revealed a great range of abnormalities in spinal cord multiple sclerosis, which related to disease course during life. Furthermore, we found very good correlation between the extent of abnormalities shown by histopathology and the SI changes on proton-density MRIs, mainly relating to demyelination revealed histopathologically.
Adult↗
Head and neck squamous cell carcinoma: US-guided fine-needle aspiration of sentinel lymph nodes for improved staging--initial experience.
Ultrasonography (US)-guided fine-needle aspiration with cytologic examination was combined with lymphoscintigraphy for the identification of sentinel lymph nodes (SLNs) in 12 patients with a squamous cell carcinoma of the oral cavity or oropharynx. Dynamic lymphoscintigraphy and a hand-held gamma probe were used to depict the SLNs to be aspirated. Cytologic examination of the aspirated SLNs revealed neck lymph node status in patients who underwent neck dissection (n = 6). In patients who underwent only transoral excision, one false-negative cytologic result was observed. This combined approach is expected to improve the detection of occult neck lymph node metastases.
Aged↗
Detection of lymph node metastases in the neck: radiologic criteria.
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Diagnostic Imaging↗
Diameter of the bony lacrimal canal: normal values and values related to nasolacrimal duct obstruction: assessment with CT.
BACKGROUND AND PURPOSE: Epiphora, or tearing due to primary acquired nasolacrimal duct obstruction (PANDO), is increasingly being treated with balloon dilatation. The cause of PANDO is unknown, but a small diameter of the bony nasolacrimal canal might be one of the etiologic factors. The purpose of this study was to determine the normal distribution of diameters of the bony canal and to ascertain whether there is an association between the diameter of the bony canal and primary nasolacrimal duct obstruction. METHODS: Using axial CT, we measured the minimum diameter of the bony nasolacrimal canal in a control group of 50 men and 50 women and in 19 patients with PANDO. RESULTS: The mean minimum diameter in the control group was 3.5 mm, which was smaller than expected on the basis of published data. The difference between the mean minimum diameter in men (3.70 mm) and that in women (3.35 mm) was significant. The mean minimum diameter in the patient group was 3.0 mm, which was significantly smaller than that in the control group. There was, however, considerable overlap. CONCLUSION: A small diameter of the bony canal appears to be one of the etiologic factors in PANDO.
Adult↗
Lymphoscintigraphy and ultrasound-guided fine needle aspiration cytology of sentinel lymph nodes in head and neck cancer patients.
Accurate staging of the regional lymph nodes is crucial for the appropriate management of patients with squamous cell carcinoma of the head and neck (HNSCC). However, the current diagnostic modalities have low accuracy for N0 neck, and even the most optimal procedure, ultrasound-guided fine needle aspiration cytology (USgFNAC), still has a sensitivity of only 42%-73%. In this study we evaluated whether the identification of the sentinel node might improve the selection of lymph nodes for USgFNAC. Twelve HNSCC patients received 3-4 peritumoral injections of 10-30 MBq 99mTc-labeled colloidal albumin, and the sentinel node was identified by dynamic scintigraphy and marked on the skin using a handheld probe, and/or by scintillation counting of the aspirates. After sentinel node identification USgFNAC was performed. Correct aspiration of the identified sentinel node(s) was confirmed by scintillation counting. In 11 out of 12 cases the sentinel node(s) could be visualized by dynamic planar imaging. In one case the sentinel node(s) were identified by scintillation counting only. In a number of patients different or supplementary lymph nodes were aspirated on the basis of sentinel node identification. These initial data strongly suggest that sentinel node identification might improve the staging of the neck by USgFNAC.
Biopsy, Needle↗