P. de Graaf

Single-Shot Turbo Spin-Echo Diffusion-Weighted Imaging for Retinoblastoma: Initial Experience

BACKGROUND AND PURPOSE: Retinoblastoma may exhibit variable hyperintensities on DWI, resulting in different values in the ADC maps, depending on their histology and cellularity. However, EP-based DWI has susceptibility artifacts and image distortions, which make DWI of the orbit a challenging technique. The aim of this study was to investigate the feasibility of single-shot turbo spin-echo (HASTE) DWI in the evaluation of children with retinoblastoma and to assess the value of ADC maps in differentiating viable and necrotic tumor tissue. MATERIALS AND METHODS: Two radiologists assessed conventional MR images, DWI, and ADC maps of 17 patients with retinoblastoma (n = 17 eyes). Non-EP DWI was performed by using a HASTE sequence with b-values of 0 and 1000 s/mm2. ADC values were measured for enhancing and nonenhancing tumor tissue. ADC maps were compared with histopathologic findings regarding tumor differentiation and viability. RESULTS: On DWI, vital tumor tissue showed hyperintensity with negligible intensity of surrounding vitreous. The difference in mean (range) ADC values between enhancing (1.03 [0.72–1.22] × 10−3 mm2 s−1) and nonenhancing (1.47 [0.99–1.80] × 10−3 mm2 s−1) parts of retinoblastoma was statistically significant (P < .0005). Nonenhancing tumor parts showed a significantly lower ADC compared with vitreous (2.67 [2.24–3.20]×10−3 mm2 s−1) (P < .0005) and subretinal fluid (2.20 [1.76–2.96] × 10−3 mm2 s−1) (P < .0005). Histopathologically, low ADC values (enhancing tumor part) correlated to viable tumor tissue, whereas intermediate ADC values (nonenhancing tumor parts) correlated to necrotic tumor tissue. CONCLUSIONS: HASTE DWI allowed adequate characterization of retinoblastoma, and ADC is a helpful tool to differentiate viable and necrotic tumor tissue and might be valuable in monitoring the response to eye-preserving therapies.

Influence of 5-aminosalicylic acid on 6-thioguanosine phosphate metabolite levels: a prospective study in patients under steady thiopurine therapy

Background and purpose:  5‐aminosalicylate (5‐ASA) raises levels of 6‐thioguanine nucleotides (6‐TGN), the active metabolites of thiopurines such as azathioprine (AZA). Changes in levels of each individual TGN – 6‐thioguanosine mono‐, di‐ and triphosphate (6‐TGMP, 6‐TGDP, 6‐TGTP) – and of 6‐methylmercaptopurine ribonucleotides (6‐MMPR) after 5‐ASA are not known.

Retinoblastoma and optic nerve enhancement on MRI: not always extraocular tumour extension

Neoadjuvant chemotherapy is useful in the management of extensive forms of retinoblastoma with radiologically detectable optic nerve invasion at diagnosis.1 Magnetic resonance imaging (MRI) can detect various degrees of optic nerve invasion as enhancement extending from an intraocular tumour into the optic nerve. However, pretreatment false positive MRI findings based on inflammation occur occasionally.2 We describe a case of unilateral retinoblastoma and false positive MRI findings of extensive optic nerve involvement. A 3 year old girl presented with retinoblastoma of the right eye. Ophthalmic examination revealed a large exophytic growing tumour, a shallow anterior chamber, rubeosis iridis, and an elevated intraocular pressure. T2WI showed a hypointense subretinal tumour mass with similar signal intensity (SI) compared to both optic nerves (fig 1A). No delineation of the ipsilateral optic nerve with surrounding cerebrospinal fluid was possible. On additional short tau inversion recovery (STIR) MRI, the optic nerve showed an increased SI from the postlaminar part to the orbital apex. Contrast enhanced T1WI showed enhancement of the tumour mass (tumour volume 2.1 cm3). Thickening and marked enhancement …

Diffusion-Weighted Imaging of the Head and Neck in Healthy Subjects: Reproducibility of ADC Values in Different MRI Systems and Repeat Sessions

BACKGROUND AND PURPOSE: DWI is typically performed with EPI sequences in single-center studies. The purpose of this study was to determine the reproducibility of ADC values in the head and neck region in healthy subjects. In addition, the reproducibility of ADC values in different tissues was assessed to identify the most suitable reference tissue. MATERIALS AND METHODS: We prospectively studied 7 healthy subjects, with EPI and TSE sequences, on 5 MR imaging systems at 3 time points in 2 institutions. ADC maps of EPI (with 2 b-values and 6 b-values) and TSE sequences were compared. Mean ADC values for different tissues (submandibular gland, sternocleidomastoid muscle, spinal cord, subdigastric lymph node, and tonsil) were used to evaluate intra- and intersubject, intersystem, and intersequence variability by using a linear mixed model. RESULTS: On 97% of images, a region of interest could be placed on the spinal cord, compared with 87% in the tonsil. ADC values derived from EPI-DWI with 2 b-values and calculated EPI-DWI with 2 b-values extracted from EPI-DWI with 6 b-values did not differ significantly. The standard error of ADC measurement was the smallest for the tonsil and spinal cord (standard error of measurement = 151.2 × 10−6 mm/s2 and 190.1 × 10−6 mm/s2, respectively). The intersystem difference for mean ADC values and the influence of the MR imaging system on ADC values among the subjects were statistically significant (P < .001). The mean difference among examinations was negligible (ie, <10 × 10−6 mm/s2). CONCLUSIONS: In this study, the spinal cord was the most appropriate reference tissue and EPI-DWI with 6 b-values was the most reproducible sequence. ADC values were more precise if subjects were measured on the same MR imaging system and with the same sequence. ADC values differed significantly between MR imaging systems and sequences.

Brain Abnormalities on MR Imaging in Patients with Retinoblastoma

BACKGROUND AND PURPOSE: Although pineoblastoma is the main brain abnormality associated with hereditary retinoblastoma, recent studies suggest an association with pineal cysts. This association is important because some pineoblastomas mimic pineal cysts. If there is a relationship, then radiologists should be aware of it because diagnostic confusion is possible. Mental retardation and congenital brain anomalies are also reported in patients with retinoblastoma, mostly in combination with 13q deletion syndrome. In this retrospective study, the presence of brain abnormalities on MR images in a large group of consecutive patients with retinoblastoma is evaluated. MATERIALS AND METHODS: Brain MR images of 168 patients with retinoblastoma from 1989 to 2009 were evaluated by 2 radiologists for tumors, structural anomalies, myelinization, and coincidental findings. Clinical records were reviewed for laterality, heredity, and the presence of the 13q deletion syndrome. RESULTS: The hereditary group (patients with bilateral and unilateral proved RB1-germline mutation) included 90 (54%) of 168 patients. Seven patients had 13q deletion syndrome. Normal findings on brain MR images were seen in 150 (89%) patients. Five pineoblastomas were detected, all in patients with hereditary retinoblastoma (5.5% in the hereditary subgroup). Nine pineal cysts were detected (2.2% in the hereditary subgroup). Corpus callosum agenesis was found in 1 patient and a Dandy-Walker variant in 1 patient, both in combination with 13q deletion syndrome. CONCLUSIONS: Pineoblastoma is associated with hereditary retinoblastoma, and structural brain abnormalities are restricted to patients with the 13q deletion syndrome. The incidence of pineal cysts in patients with retinoblastomas is similar to that in healthy children and is not associated with hereditary retinoblastoma.

Contrast-Enhancement of the Anterior Eye Segment in Patients with Retinoblastoma: Correlation between Clinical, MR Imaging, and Histopathologic Findings

BACKGROUND AND PURPOSE: AES contrast-enhancement is recognized in a substantial number of retinoblastoma-affected eyes. We retrospectively investigated the histopathologic basis of AES contrast-enhancement on MR images in retinoblastoma. MATERIALS AND METHODS: Pretreatment contrast-enhanced MR images were obtained from 42 children with retinoblastoma. Forty-two enucleated eyes were included in this study, AES enhancement was evaluated by using a 3-point score, and these data were correlated with clinical, MR imaging, and histopathologic findings. Additionally, 14 specimens were immunohistochemically analyzed for CD31, VEGF, and Flt-1 expression. Statistical correlations with AES enhancement were assessed by using a linear-by-linear association test and univariate and multivariate ordinal regressions. RESULTS: The degree of abnormal AES enhancement was moderate in 15 (36%) eyes and strong in 14 (33%) eyes, whereas 13 (31%) eyes showed normal AES enhancement. In multivariate analysis, the degree of AES enhancement showed statistically significant correlations with iris surface-vessel count (P = .05) and optic nerve invasion (P = .04) in the enucleated eye and with tumor volume (P = .02) as detected on MR imaging. No significant associations between AES enhancement and VEGF expression in the iris were observed. Flt-1 (P = .04) staining in iris stroma and IA as detected with CD31 staining (P = .009) both yielded a statistically significant positive correlation with abnormal AES enhancement. CONCLUSIONS: The degree of abnormal AES enhancement on MR imaging in retinoblastoma reflects angiogenesis in the iris. AES enhancement is also a hallmark of advanced retinoblastoma because its degree correlates with tumor volume and optic nerve invasion.

Retinoblastoma: Value of Dynamic Contrast-Enhanced MR Imaging and Correlation with Tumor Angiogenesis.

Fifteen patients with retinoblastoma were assessed with dynamic contrast-enhanced MRI over a period of 8 minutes; late contrast enhancement was also studied. The authors found that during the early phase of the perfusion studies the time curve correlated with microvessel density whereas late enhancement correlated with tumor necrosis. Thus, dynamic contrast-enhanced MRI may be used to assess angiogenesis and necrosis and may be used to monitor treatment. BACKGROUND AND PURPOSE: Noninvasive evaluation of retinoblastoma treatment response has become more important due to increased use of eye-sparing treatments. We evaluated the relation between DCE-MR imaging and histopathologic parameters to determine the value of DCE-MR imaging in assessing tumor angiogenesis and prognostic features. MATERIALS AND METHODS: Fifteen consecutive patients with retinoblastoma (mean age, 24 months; range, 2–70 months) undergoing enucleation as the primary treatment (15 eyes) were scanned at 1.5T by using dedicated surface coils. Pretreatment DCE-MR imaging of the most affected eye was evaluated by 2 observers by using curve-pattern analysis, with the first 5 minutes of each curve and the full time-series described as κ5min and κ17min, respectively. Assessed histopathologic and immunologic parameters included optic nerve invasion, choroid invasion, MVD, tumor necrosis, and expression of VEGF and Flt-1. RESULTS: The median value of κ5min was 1.28 (range, 0.87–2.07) and correlated positively with MVD (P = .008). The median value of κ17min was 1.33 (range, 0.35–3.08) and correlated negatively with tumor necrosis (P = .002). Other histopathologic and immunohistopathologic parameters did not correlate with DCE-MR imaging parameters. Interobserver agreement was 0.53 for κ5min and 0.91 for κ17min. CONCLUSIONS: In retinoblastoma, the early phase of the DCE time curve positively correlates with MVD, while the presence of late enhancement is correlated with necrosis. Thus, the potential for DCE-MR imaging to noninvasively assess tumor angiogenesis and necrosis in retinoblastoma is promising and warrants further investigation.

Retinal Dysplasia Mimicking Intraocular Tumor: MR Imaging Findings with Histopathologic Correlation

SUMMARY: We report a 6-month-old boy who presented with unilateral leukocoria, retinal detachment, and a retrolental mass in a microphthalmic eye based on retinal dysplasia with concurrent optic nerve aplasia. Dysplastic retinal tissue, a rare congenital defect, may create a clinical and radiologic picture of an intraocular mass closely resembling tumor tissue. MR imaging findings with histopathologic correlation are presented to facilitate discrimination of the more common causes of leukocoria.

Quantitative Diffusion-Weighted MRI Parameters and Human Papillomavirus Status in Oropharyngeal Squamous Cell Carcinoma

BACKGROUND AND PURPOSE: Patients with human papillomavirus–positive oropharyngeal squamous cell carcinomas have a better survival rate than those with human papillomavirus–negative oropharyngeal squamous cell carcinomas. DWI characterizes biologically relevant tumor features, and the generated ADC may also provide prognostic information. We explored whether human papillomavirus status and ADC values are independent tumor characteristics. MATERIALS AND METHODS: Forty-four patients with oropharyngeal squamous cell carcinomas underwent pretreatment DWI. ADC values for the primary tumors were determined by using 3 b-values in an ROI containing the largest area of solid tumor on a single section of an axial DWI image. Human papillomavirus status was determined with p16 immunostaining, followed by high-risk human papillomavirus DNA detection on the p16-positive cases. RESULTS: Twenty-two patients were human papillomavirus–positive (50.0%). ADC values were not significantly different between human papillomavirus–negative (ADCmean = 1.56 [1.18–2.18] × 103 mm2/s) and human papillomavirus–positive tumors (ADCmean = 1.46 [1.07–2.16] × 103 mm2/s). CONCLUSIONS: No significant association between ADC and human papillomavirus status was found in oropharyngeal squamous cell carcinomas. In our study population, differences in genetic and histologic features between human papillomavirus–positive and human papillomavirus–negative oropharyngeal squamous cell carcinomas did not translate into different ADC values. Long-term follow-up studies are needed to establish whether ADC has prognostic value and whether this is independent of the human papillomavirus status.

Detection of Calcifications in Retinoblastoma Using Gradient- Echo MR Imaging Sequences: Comparative Study between In Vivo MR Imaging and Ex Vivo High-Resolution CT

BACKGROUND AND PURPOSE: Intratumoral calcifications are very important in the diagnosis of retinoblastoma. Although CT is considered superior in detecting calcification, its ionizing radiation, especially in patients with hereditary retinoblastoma, should be avoided. The purpose of our study was to validate T2*WI for the detection of calcification in retinoblastoma with ex vivo CT as the criterion standard. MATERIALS AND METHODS: Twenty-two consecutive patients with retinoblastoma (mean age, 21 months; range, 1–71 months) with enucleation as primary treatment were imaged at 1.5T by using a dedicated surface coil. Signal-intensity voids indicating calcification on T2*WI were compared with ex vivo high-resolution CT, and correlation was scored by 2 independent observers as poor, good, or excellent. Other parameters included the shape and location of the signal-intensity voids. In 5 tumors, susceptibility-weighted images were evaluated. RESULTS: All calcifications visible on high-resolution CT could be matched with signal-intensity voids on T2*WI, and correlation was scored as excellent in 17 (77%) and good in 5 (23%) eyes. In total, 93% (25/27) of the signal-intensity voids inside the tumor correlated with calcifications compared with none (0/8) of the signal-intensity voids outside the tumor. Areas of nodular signal-intensity voids correlated with calcifications in 92% (24/26), and linear signal-intensity voids correlated with hemorrhage in 67% (6/9) of cases. The correlation of signal-intensity voids on SWI was better in 4 of 5 tumors compared with T2*WI. CONCLUSIONS: Signal-intensity voids on in vivo T2*WI correlate well with calcifications on ex vivo high-resolution CT in retinoblastoma. Gradient-echo sequences may be helpful in the differential diagnosis of retinoblastoma. The combination of funduscopy, sonography, and high-resolution MR imaging with gradient-echo sequences should become the standard diagnostic approach for retinoblastoma.