Changes In Contrast Enhancement Research Articles

DDEL-11. DETERMINING THE DOSE OF REGADENOSON MOST LIKELY TO TRANSIENTLY ALTER THE INTEGRITY OF THE BLOOD-BRAIN BARRIER IN PATIENTS WITH GLIOMAS

Abstract BACKGROUND The blood brain barrier (BBB) is a major obstacle to the delivery of chemotherapy to the CNS. Regadenoson is an FDA approved adenosine A2 agonist used for cardiac stress tests. In murine models, it transiently increases BBB permeability to a 70KD dextran. This multi-institutional, NIH funded, Adult Brain Tumor Consortium trial was designed to discover a dose of regadenoson that substantially increases vascular permeability in normal appearing white matter (NAWM) where drug delivery is particularly challenging. METHODS Adults ages 18-45 with supratentorial gliomas at low-risk for regadenoson complications were recruited (n = 7). One patient was treated at each of seven dose levels (from 0.05 to 1.4 mg) that are known to be safe in humans. The primary outcome measure is change in vascular permeability via dynamic contrast enhanced (DCE) perfusion MRI estimates of Ktrans. The primary outcome measure was a 10-fold higher Ktrans in NAWM than reported in literature (Ktrans > 0.04 min-1). Contrast-enhanced T1 subtraction map estimates of change in contrast enhancement and other measurements in normal brain and non-enhancing tumor were quantified. RESULTS Ktrans measures in NAWM averaged 1.13x10-3 ± 0.44x10-3 (SEM) min-1, lower than the target of 0.04 min-1. Normalized, contrast enhanced T1-weighted MR signal intensity in NAWM increased an average of 74.0 ± 22.4% min-1 (SEM) min-1, which was significantly higher than zero (P = 0.0163). Data available from this limited sample failed to meet the target goal in Ktrans increase or change in contrast enhancing signal intensity. CONCLUSION Administration of regadenoson at seven different doses did not significantly elevate Ktrans for gadolinium in NAWM. This data suggests that single doses of regadenoson are unlikely to substantially increase the delivery of therapeutic agents in non-enhancing brain tissue. This trial design is appropriate for further human testing of other regadenoson schedules and other novel approaches aimed at transiently modifying BBB permeability.

Solitary Fibrous Tumor of Orbit: Changes of Tumor Size and Tumor Contrast Enhancement

Purpose: To report a case of solitary fibrous tumor of the orbit in a patient with changes in tumor size and contrast enhancement.Case summary: A 64-year-old male patient presented with dizziness, discomfort on eye movement, anosmia, and proptosis. Orbital computed tomography showed an enhancing mass in the right extraconal space, lateral to the medial rectus and inferior to the superior oblique muscle. The mass appeared to be a cavernous hemangioma and the patient was monitored for changes in mass size and eye movements. After 24 months of follow-up, the mass size and symptoms of right eyelid swelling, proptosis, and diplopia had increased. Excision and biopsy of the mass were performed under general anesthesia. The biopsy confirmed that the mass was a solitary fibrous tumor. The postoperative period was uneventful and no recurrence was observed at 6 months after surgery.Conclusions: Solitary fibrous tumor is a soft tissue tumor that rarely occurs in the orbit, and should be considered in cases with an intraorbital mass accompanied by increased size and changes in contrast enhancement on imaging.

Primary intramedullary spinal cord pilocytic astrocytoma with anaplasia in an adult: illustrative case.

BACKGROUNDPrimary intramedullary spinal cord (IMSC) pilocytic astrocytoma (PA) with anaplasia is extremely rare.OBSERVATIONSA 50-year-old man presented to our hospital with numbness of the left posterior rib region, back, and bilateral lower limbs. Contrast-enhanced T1-weighted magnetic resonance imaging (MRI) revealed an intramedullary lesion at T2–T3 with no contrast enhancement. The patient opted for conservative treatment. Eighteen months after the first consultation, the patient presented with slowly progressive numbness of the bilateral upper limbs, paraparesis, and dysuria, with rapid deterioration over the following 3 months. T1- and T2-weighted MRI revealed expansion of the intramedullary lesion, which extended from C7 to T5, and syringomyelia at C5–C6. Contrast-enhanced T1-weighted MRI revealed an enhancing intramedullary lesion at C7–T5. Open biopsy and C5–T5 laminectomy were performed for diagnosis and decompression. PA with anaplasia was diagnosed based on pathological and immunohistochemical findings. The patient received postoperative radiotherapy and chemotherapy.LESSONSRapidly progressive IMSC PA with a change in contrast enhancement is extremely rare in adults. PA may undergo a spontaneous malignant transformation during its natural clinical course. In this case, the change in contrast enhancement may have been associated with the malignant transformation of the PA.

Estimation of cardiac output from test-bolus during coronary computed tomography angiography: a personalized mathematical model

Abstract Background Contrast enhancement is measured in the aorta at set intervals of time during the test-bolus series of a coronary computed tomography angiography [CCTA]. Its primary purpose is to ascertain the timing delay of the main scan after contrast administration to ensure optimal image acquisition. The change in contrast enhancement over time correlates directly with contrast medium concentration in the vessel. If the complete time density curve [TDC] is known and corrected for contrast enhancement due to recirculation it can be used to estimate the cardiac output [CO], by e.g. a modified Stewart-Hamilton equation, as shown by Mahnken et al. Purpose The current study aims to explore ways to improve the mathematical estimation of CO. In practical applications only part of the TDC is known. By integrating patient factors, contrast factors and scanning factors with a mathematical compartment model, the CO can be estimated. Estimated CO is subsequently used to simulate the distribution of contrast medium in the body, enabling prospective adjustment of contrast medium administration protocol that could be tailored to each individual, utilizing the lowest possible dose of contrast to achieve diagnostically acceptable CCTA images. Methods Test-bolus images were acquired sequentially at two second intervals over the aorta from 40 patients with a clinical indication for CCTA. According to clinical routines, premedication with beta-blockers was performed in 35 patients and sublingual nitroglycerine in 39 patients. Attenuation in the aorta was measured by a centrally placed region of interest with a width of half the aortic diameter. Each participant underwent cardiac magnetic resonance imaging [MRI] immediately after CCTA, from which actual CO was measured as a method of validation. A mathematical compartment model for distribution of contrast, outlined by Bae et al. was improved and used to estimate the CO from the TDC in the aorta during the test-bolus. The estimated CO [COEst] was compared with CO calculated from MRI [COMR], and estimated attenuation in the aorta [HUEst] was compared with measured attenuation in the aorta during test-bolus in CCTA [HUCT]. Results One patient was excluded due to unacceptable cardiac MRI. Our model showed a strong correlation between COEst and COMR for all patients (r=0.62, p<0.001) and a higher correlation for women than men when separated by gender (men r=0.58, p=0.006; women r=0.63, p=0.005). Women had an average COEst 1.92 L/min significantly lower than men (p<0.001), despite no statistical difference in COMR between men and women. Conclusion An improved mathematical model for estimation of CO can be a valuable tool to improve individualized contrast administration protocols and increase the diagnostic information extracted from a CCTA. In addition to known physical factors it is clear that gender and weight, including their derivatives, must play a more significant role in estimation. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Stavanger University Hospital

Tumor Contrast-Enhancement for Monitoring of PRRT 177Lu-DOTATATE in Pancreatic Neuroendocrine Tumor Patients

Background: Therapy monitoring of cancer treatment by contrast-enhanced CT (CECT), applying response evaluation criteria in solid tumors criteria version 1. 1 (RECIST 1.1) is less suitable for neuroendocrine tumors (NETs) which, when responding, tend to show stabilization rather than shrinkage. New methods are needed to further classify patients in order to identify non-responders at an early stage and avoid unnecessary adverse effects and costs. Changes in arterial tumor attenuation and contrast-enhancement could be used to identify the effect of therapy, perhaps even in early stages of treatment.Methods: Patients with metastatic pancreatic NETs (PNETs) receiving peptide receptor radionuclide therapy (PRRT) with 177Lu-DOTATATE underwent CECT at baseline, mid-treatment (PRRT cycles 3–5) and at follow-up, 3 months after the last PRRT cycle. At baseline CECT, the liver metastasis with the highest arterial attenuation was identified in each patient. The fold changes in arterial tumor attenuation (Hounsfield Units, HU), contrast-enhancement (HU), and transversal tumor area (cm2) between CECT at baseline, mid-treatment and follow-up were calculated. Correlation of the tumor metrics to outcome parameters such as progression-free survival (PFS) and time to best response was performed.Results: Fifty-two patients were included (27 men, 25 women), median age 60 years (range 29–80), median Ki-67 8% (range 1–30). Six patients had grade 1 PNETs, forty had grade 2 and four had grade 3 tumors. As an internal control, it was first tested and established that the tumor contrast-enhancement was not merely related to that of the abdominal aorta. The mean ± SD arterial attenuation of the liver metastases was similar at baseline, 217 ± 62 HU and at mid-treatment, 238 ± 80 HU and then decreased to 198 ± 62 HU at follow-up, compared to baseline (p = 0.024, n = 52) and mid-treatment (p = 0.0004, n = 43). The transversal tumor area decreased 25% between baseline and follow-up (p = 0.013, n = 52). Tumor contrast-enhancement increased slightly from baseline to mid-treatment and these fold changes correlated with PFS (R2 = 0.33, p = 0.0002, n = 37) and with time to best response (R2 = 0.34, p < 0.0001, n = 37).Conclusions: Early changes in contrast-enhancement and arterial attenuation in PNET liver metastases may for CECT monitoring of PRRT yield complementary information to evaluation by RECIST 1.1.

Abstract P1-10-06: Radiomic measurements of tumor-associated vasculature morphology and function on pretreatment dynamic MRI identifies responders to neoadjuvant chemotherapy

Abstract Background: Angiogenesis is crucial to a tumor's growth and an important factor in therapeutic outcome. Although quantitative analysis of tumors on dynamic contrast enhanced (DCE) MRI can provide indirect characterization of a tumor's vascularization, direct computational analysis of the tumor-associated vessel network remains a promising, but under-explored potential marker of therapeutic response. For instance, surrounding vasculature with a convoluted 3-dimensional shape and poor blood flow may indicate a more aggressive tumor and poorly facilitate delivery of therapeutic agents. In this work, we present a computational approach for the prediction of neoadjuvant chemotherapy response using quantitative imaging features describing the morphology and function of tumor associated vasculature on pretreatment MRI. Methods: 243 patients who received DCE-MRI scans prior to neo-adjuvant chemotherapy (NAC) at institution A [n=83], B [n=76], or one of nine other institutions as part of the ISPY1 Trial [n=84] were divided randomly into training (n=123) and testing (n=120) sets. 148 patients were HER2- and received neoadjuvant AC-T, while the 95 HER2+ patients were treated with TCHP (ISPY predates anti-HER2 therapy and HER2+ ISPY patients were excluded). 79 patients achieved pathological complete response [pCR, ypT0/is] following NAC. MRI exams were collected with a 1.5 or 3 Tesla scanner in the axial or sagittal plane. A baseline scan and 2-5 scans after injection of a gadolinium-based contrast agent with a median temporal resolution of 2.5 minutes were acquired. A portion of the tumor was manually delineated, then semi-automatically expanded to 3D. Vasculature was isolated from subtraction images with a specialized filtering approach to detect vessel-shaped objects. Features describing the 3D shape and architecture of the tumor-associated vessel network (e.g. curvature, torsion, and local orientation) and functional semi-quantitative pharmacokinetic (PK) measurements of temporal contrast enhancement changes (e.g. signal enhancement ratio, time to peak enhancement, and rates of uptake and washout) were calculated. Performance was assessed by area under the receiver operating characteristic curve (AUC), as well as the accuracy, sensitivity, and specificity at the operating point corresponding to the Youden Index. The most discriminating features were determined based on frequency of selection by the random forest classifier. Results: Within the training set, PK parameters of the vessels (AUC=.66) outperformed relative to the PK of tumor (AUC=.63) and the PK of peritumoral regions (AUC=.64); however, a combination of the three yielded best performance (AUC=.75). Vessel shape features alone achieved AUC=.67 in the training set. When multi-region PK features and tumor shape features were combined and applied to the 120-patient independent testing set, the random forest classifier achieved an AUC of 0.70 and identified 81% of patients who would achieve pCR. Non-pCR was best characterized by increased vessel curvature and PK parameters indicating poor perfusion, such as greater time to peak enhancement, slower uptake rate, and quicker washout. Conclusions: Our findings suggest that properties of the tumor-associated vessel network, such as its shape and enhancement profile, might provide value in identifying patients who will respond to NAC before administration of treatment. Accuracy (%)Sensitivity (%)Specificity (%)Full testing set (n=120)678160HER2+ (n=44)709548HER2- (n=76)646365HER2-, HR+ (n=51)678364Triple Negative (n=25)605067 Citation Format: Nathaniel Braman, Prateek Prasanna, Kaustav Bera, Mehdi Alilou, Manasa Vulchi, Maryam Etesami, Paulette Turk, Jame Abraham, Donna Plecha, Anant Madabhushi. Radiomic measurements of tumor-associated vasculature morphology and function on pretreatment dynamic MRI identifies responders to neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-10-06.

High-grade soft-tissue sarcoma: optimizing injection improves MRI evaluation of tumor response.

To determine the acquisition delay after gadolinium-chelate injection that optimizes the prediction of the histological response during anthracycline-based neoadjuvant chemotherapy (NAC) for locally advanced high-grade soft-tissue sarcomas (STS). Thirty patients (mean age 62 years) were included in this IRB-approved study. All patients received 5-6 cycles of NAC followed by surgery. A good response was defined as ≤ 10% viable cells on histological analysis of the surgical specimen. DCE-MRI was performed before treatment (MRI0) and after two cycles (MRI1). Images were obtained every 8 s. Change in contrast enhancement (CE) between MRI0 and MRI1 was calculated for each acquisition delay 't' on the whole tumor volume. Area under the receiver-operating characteristics curves (AUROC) for change in CE was calculated at each acquisition delay, as well as the accuracy of the Choi criteria. There were 22 (73.3%) poor responders. Acquisition delay had a significant effect on change in CE and on the response status according to Choi (p = 0.0014 and 0.0270, respectively). The highest AUROC was obtained at t = 58 s (0.792) with an optimal threshold of a -30.5% decrease in CE. At t = 58 s, accuracy to predict a poor response was 82.8% above this threshold, while it was 72.4% and 70% with no objective response according to the Choi criteria and RECIST1.1, respectively. Optimization of acquisition delay after injection to estimate change in CE improves the prediction of histological response. For STS undergoing NAC, a 60-s delay can be recommended with MRI. • Accuracy of response criteria based on contrast enhancement, like the Choi criteria, is dependent on the acquisition delay after gadolinium-chelate injection. • DCE-MRI helps determine the optimal acquisition delay after gadolinium-chelate injection for improving evaluation of tumor response. • In soft tissue sarcoma, an acquisition delay at 60 s optimizes the evaluation of the response and accuracy of the Choi criteria.

Response Assessment in Neuro-Oncology criteria, contrast enhancement and perfusion MRI for assessing progression in glioblastoma.

The purpose of the study was to evaluate Response Assessment in Neuro-Oncology (RANO) criteria in glioblastoma multiforme (GBM), with respect to the Macdonald criteria and changes in contrast-enhancement (CE) volume. Related variations in relative cerebral blood volume (rCBV) were investigated. Forty-three patients diagnosed between 2006 and 2010 were included. All underwent surgical resection, followed by temozolomide-based chemoradiation. MR images were retrospectively reviewed. Times to progression (TTPs) according to RANO criteria, Macdonald criteria and increased CE volume (CE-3D) were compared, and the percentage change in the 75th percentile of rCBV (rCBV75) was evaluated. After a median follow-up of 22.7months, a total of 39 patients had progressed according to RANO criteria, 32 according to CE-3D, and 42 according to Macdonald. Median TTPs were 6.4, 9.3, and 6.6months, respectively. Overall agreement was 79.07% between RANO and CE-3D and 93.02% between RANO and Macdonald. The mean percentage change in rCBV75 at RANO progression onset was over 73% in 87.5% of patients. In conclusion, our findings suggest that CE-3D criterion is not yet suitable to assess progression in routine clinical practice. Indeed, the accurate threshold is still not well defined. To date, in our opinion, early detection of disease progression by RANO combined with advanced MRI imaging techniques like MRI perfusion and diffusion remains the best way to assess disease progression. Further investigations that would examine the impact of treatment modifications after progression determined by different criteria on overall survival would be of great value.

Textural analysis of early-phase spatiotemporal changes in contrast enhancement of breast lesions imaged with an ultrafast DCE-MRI protocol.

New ultrafast view-sharing sequences have enabled breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to be performed at high spatial and temporal resolution. The aim of this study is to evaluate the diagnostic potential of textural features that quantify the spatiotemporal changes of the contrast-agent uptake in computer-aided diagnosis of malignant and benign breast lesions imaged with high spatial and temporal resolution DCE-MRI. The proposed approach is based on the textural analysis quantifying the spatial variation of six dynamic features of the early-phase contrast-agent uptake of a lesion's largest cross-sectional area. The textural analysis is performed by means of the second-order gray-level co-occurrence matrix, gray-level run-length matrix and gray-level difference matrix. This yields 35 textural features to quantify the spatial variation of each of the six dynamic features, providing a feature set of 210 features in total. The proposed feature set is evaluated based on receiver operating characteristic (ROC) curve analysis in a cross-validation scheme for random forests (RF) and two support vector machine classifiers, with linear and radial basis function (RBF) kernel. Evaluation is done on a dataset with 154 breast lesions (83 malignant and 71 benign) and compared to a previous approach based on 3D morphological features and the average and standard deviation of the same dynamic features over the entire lesion volume as well as their average for the smaller region of the strongest uptake rate. The area under the ROC curve (AUC) obtained by the proposed approach with the RF classifier was 0.8997, which was significantly higher (P=0.0198) than the performance achieved by the previous approach (AUC=0.8704) on the same dataset. Similarly, the proposed approach obtained a significantly higher result for both SVM classifiers with RBF (P=0.0096) and linear kernel (P=0.0417) obtaining AUC of 0.8876 and 0.8548, respectively, compared to AUC values of previous approach of 0.8562 and 0.8311, respectively. The proposed approach based on 2D textural features quantifying spatiotemporal changes of the contrast-agent uptake significantly outperforms the previous approach based on 3D morphology and dynamic analysis in differentiating the malignant and benign breast lesions, showing its potential to aid clinical decision making.

Dynamic Contrast-Enhanced Ultrasound of Colorectal Liver Metastases as an Imaging Modality for Early Response Prediction to Chemotherapy.

Our aim was to investigate whether dynamic contrast-enhanced ultrasound (DCE-US) can detect early changes in perfusion of colorectal liver metastases after initiation of chemotherapy. Newly diagnosed patients with colorectal cancer with liver metastases were enrolled in this explorative prospective study. Patients were treated with capecitabine or 5-fluorouracil-based chemotherapy with or without bevacizumab. DCE-US was performed before therapy (baseline) and again 10 days after initiation of treatment. Change in contrast-enhancement in one liver metastasis (indicator lesion) was measured. Treatment response was evaluated with a computed tomography (CT) scan after three cycles of treatment and the initially observed DCE-US change of the indicator lesion was related to the observed CT response. Eighteen patients were included. Six did not complete three series of chemotherapy and the evaluation CT scan, leaving twelve patients for analysis. Early changes in perfusion parameters using DCE-US did not correlate well with subsequent CT changes. A subgroup analysis of eight patients receiving bevacizumab, however, demonstrated a statistically significant correlation (p = 0.045) between early changes in perfusion measures of peak enhancement at DCE-US and tumor shrinkage at CT scan. The study indicates that early changes in DCE-US perfusion measures may predict subsequent treatment response of colorectal liver metastases in patients receiving bevacizumab.

Desmoid fibromatosis: MRI features of response to systemic therapy.

Imaging criteria for measuring the response of desmoid fibromatosis to systemic therapy are not well established. We evaluated a series of patients with desmoids who underwent systemic therapy to document magnetic resonance imaging (MRI) features associated with a positive clinical response. This Institutional Review Board-approved retrospective study included 23 patients (mean age 40.5) with 29 extra-abdominal tumors. Therapeutic regimens included cytotoxic chemotherapy (n = 19), targeted therapy (n = 3), and nonsteroid anti-inflammatory drugs (NSAIDS; n = 1). Clinical effects were categorized as progressive disease, stable, or partial response. Maximum tumor dimension (Dmax), approximate tumor volume (VTumor), and quantitative tumor T2 hyperintensity and contrast enhancement (relative to muscle) for pre- and post-treatment MRIs were compared. Three lesions progressed, 5 lesions were stable, whereas 21 showed a clinical response. Dmax decreased more in responders (mean -11.0%) than in stable/progressive lesions (mean -3.6 and 0% respectively, p = 0.28, ANOVA); by Response Evaluation Criteria in Solid Tumors (RECIST 1.1) 27 out of 29 lesions were "stable," including the 3 progressive lesions. In responders, VTumor change averaged -29.4%, but -19.2% and +32.5% in stable and progressive lesions respectively (p = 0.002, ANOVA); by 3D criteria 14 out of 29 lesions showed a partial response. T2 hyperintensity decreased by 50-54% in partial response/stable disease, but only by 10% in progressive lesions (p = 0.049, t test). Changes in contrast enhancement ranged from -23% to 0%, but were not statistically significant among response groups (p = 0.37). Change in T2 hyperintensity showed a positive correlation with volumetric change (r = 0.40). Decreases in volume and T2 hyperintensity reflect the positive response of desmoid fibromatosis to systemic therapy; RECIST 1.1 criteria are not sensitive to clinically determined tumor response.

Circulatory dynamics of the cauda equina in lumbar canal stenosis using dynamic contrast-enhanced magnetic resonance imaging

Background contextThere has been no study regarding the cauda equina circulation of patients with neurogenic intermittent claudication (NIC) in lumbar spinal canal stenosis (LSCS) using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). PurposeThe mechanism responsible for the onset of NIC was investigated using DCE-MRI to examine changes in cauda equina blood flow in patients with LSCS. Study designThis was a retrospective longitudinal registry and magnetic resonance imaging study. Patient sampleThe subjects consisted of 23 patients who had LSCS associated with NIC (stenosis group). Ten asymptomatic volunteers who did not have NIC served as controls (control group). In the LSCS group, the cross-sectional area of the dural sac was < 75 mm2 at the site of most severe stenosis. These patients were further divided into single and double stenosis subgroups. Outcome measuresThe main measures we used were the signal intensity (S-I) ratio and the shape and size of the time intensity (T-I) curves. We compared these between the stenosis and control groups. MethodsAt first, plain T1-weighted MR images were obtained and the lumbar dural sac cross-sectional area was measured using a digitizer. For DCE-MRI, sagittal T1-weighted images of the same slice were acquired continuously for 10 minutes after administration of gadolinium as an intravenous bolus to observe the distribution of contrast medium (gadolinium) in the cauda equina. To objectively evaluate changes in contrast enhancement of the cauda equina at the site of canal stenosis, regions of interest were established. The signal intensity (SI) ratio was calculated to compare the signal intensities before and after contrast enhancement, and time-intensity curves were prepared to investigate changes over time. ResultsThe static imaging findings and the changes of gadolinium uptake showed striking differences between the study and control patients. In the stenosis group, abnormal intrathecal enhancement showed around the site of stenosis on enhanced MR imaging. The SI ratio at the site of canal stenosis had a slower increase in the arterial phase when compared with that in the control group and remained high in the venous phase for up to 10 minutes. Finally, abnormal intrathecal enhancement was visible around the site of stenosis on enhanced MR imaging in all patients. ConclusionsThese clinical data indicate that cauda equina nerve roots in the LSCS patients are pathologic even when symptoms are not elicited in the supine position, suggesting that intraradicular venous congestion and edema themselves do not influence the existence of radicular symptoms.

Selective X-ray contrast enhancement of the spleen of living mice mediated by gold nanorods.

Gold nanomaterials (AuNPs) represent a promising new class of contrast agents for X-ray computed tomographic (CT) imaging in both research and clinical settings. These materials exhibit superior X-ray absorption properties compared with other iodinated agents, and thus require lower injection doses. Gold is nonimmunogenic and therefore contributes to safety profile in living specimens. Unfortunately, most reports on the use of AuNPs as X-ray CT enhancers only demonstrate marginal enhancement of the intended anatomical structure. In this study, we demonstrate the dramatic properties of gold nanorods (GNR) to serve as robust X-ray CT contrast-enhancing agent for selective imaging of the spleen. These organ-specific uptake properties were delineated by performing longitudinal CT imaging of living mice that were dosed with GNR at 2 day intervals. Rapid uptake in spleen was noted within 12 h of first systemic administration with a change in contrast enhancement of 90 Hounsfield units (ΔHU = 90) and with two subsequent injections a total contrast enhancement of over 200 HU was observed. The resulting images provide excellent contrast that will enable the detailed anatomical visualization and study of a range of pre-clinical models of spleen disease including infection and cancer.

Role of O-(2-18F-Fluoroethyl)-l-Tyrosine PET as a Diagnostic Tool for Detection of Malignant Progression in Patients with Low-Grade Glioma

In patients with low-grade glioma (LGG) of World Health Organization (WHO) grade II, early detection of progression to WHO grade III or IV is of high clinical importance because the initiation of a specific treatment depends mainly on the WHO grade. In a significant number of patients with LGG, however, information on tumor activity and malignant progression cannot be obtained on the basis of clinical or conventional MR imaging findings only. We here investigated the potential of O-(2-(18)F-fluoroethyl)-L-tyrosine ((18)F-FET) PET to noninvasively detect malignant progression in patients with LGG. Twenty-seven patients (mean age ± SD, 44 ± 15 y) with histologically proven LGG (WHO grade II) were investigated longitudinally twice using dynamic (18)F-FET PET and routine MR imaging. Initially, MR imaging and PET scans were performed, and diagnosis was confirmed on the basis of biopsy. Subsequently, PET scans were obtained when clinical findings or contrast-enhanced MR imaging suggested malignant progression. Maximum and mean tumor-to-brain ratios (20-40 min after injection) (TBRmax and TBRmean, respectively) of (18)F-FET uptake as well as tracer uptake kinetics (i.e., time to peak [TTP] and patterns of the time-activity curves) were determined. The diagnostic accuracy of imaging parameters for the detection of malignant progression was evaluated by receiver-operating-characteristic analyses and by Fisher exact test for 2 × 2 contingency tables. In patients with histologically proven malignant progression toward WHO grade III or IV (n = 18), TBRmax and TBRmean increased significantly, compared with baseline (TBRmax, 3.8 ± 1.0 vs. 2.4 ± 1.0; TBRmean, 2.2 ± 0.3 vs. 1.6 ± 0.6; both P < 0.001), whereas TTP decreased significantly (median TTP, 35 vs. 23 min; P < 0.001). Furthermore, time-activity curve patterns changed significantly in 10 of 18 patients (P < 0.001). The combined analysis of (18)F-FET PET parameters (i.e., changes of TBRmax, TTP, or time-activity curve pattern) yielded a significantly higher diagnostic accuracy for the detection of malignant progression than changes of contrast enhancement in MR imaging (accuracy, 81% vs. 63%; P = 0.003). Both tumor-to-brain ratio and kinetic parameters of (18)F-FET PET uptake provide valuable diagnostic information for the noninvasive detection of malignant progression of LGG. Thus, repeated (18)F-FET PET may be helpful for further treatment decisions.

Earlier Diagnosis of Progressive Disease during Bevacizumab Treatment Using O-(2-18F-Fluorethyl)-L-Tyrosine Positron Emission Tomography in Comparison with Magnetic Resonance Imaging

Antiangiogenic treatment using bevacizumab in brain tumor patients may cause difficulties in the diagnosis of tumor progression (ie, nonenhancing tumor progression). Newly defined criteria for treatment assessment and diagnosis of tumor progression (ie, RANO [Response Assessment in Neuro-Oncology] criteria) have implemented signal alterations on T2/fluid-attenuated inversion recovery (FLAIR) sequences to changes in contrast enhancement. However, T2/FLAIR hyperintensity may be influenced by other causes (eg, radiation-induced leukoencephalopathy, peritumoral edema, gliosis). Positron emission tomography using the radiolabeled amino acid O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET-PET) may help detect the metabolically active tumor extent. We present 18F-FET-PET imaging findings in a glioblastoma patient during bevacizumab treatment suggesting an earlier diagnosis of tumor progression than magnetic resonance imaging changes, which are based on the RANO criteria.

Radiosurgery for Metastatic Spinal Tumors: Follow-Up MR Findings

MR imaging is the primary tool for evaluation and monitoring of spinal tumors. We retrospectively analyzed the MR imaging findings before and after SRS for metastatic spinal tumors. We reviewed MR imaging findings on 79 metastatic spinal tumor lesions in 44 patients (29 male and 15 female)who had undergone radiosurgery between November 2003 and April 2008. Posttreatment MR imaging was evaluated retrospectively for 3 aspects: 1) changes in tumor volume; 2) changes in T2 signal intensity;and 3) changes in contrast enhancement patterns. With regard to tumor volume on MR images, 32 lesions(40.5%) decreased in volume (group 1), 39 (49.4%) showed no change (group 2), and 8 (10.1%) increased in volume (group 3). T2 signal intensities were unchanged in 4 lesions (type 1), homogeneously increased in 3 (type 2), and changed to a homogeneously dark signal in 4 (type 4). The T2 signal intensity was increased and inter mixed with dark signal intensity (type 3) in 68 lesions. A decrease in contrast enhancement with or without non-enhancing foci was seen in 73 lesions. A persistent homogeneous enhancement pattern was seen in all 4 of the type 1 lesions, in 1 of the 3 type 2 lesions, and in 1 of the 68 type 3 lesions. Main MR imaging features of locally controlled metastatic spinal tumors included no increase in tumor volume, increased T2 signal intensity with intermixed T2 dark signal intensity,and decreased contrast enhancement. Follow-up MR imaging also provided several patterns of tumor recurrence [corrected].

Peptide receptor radionuclide therapy as a potential tool for neoadjuvant therapy in patients with inoperable neuroendocrine tumours (NETs)

PurposeNeuroendocrine tumours (NET) are a heterogeneous group of neoplasms of diffuse neuroendocrine cells. Surgery is the main aim in the treatment of NETs, which becomes impossible in the case of large tumours or infiltration into other tissues and/or important blood vessels. Neoadjuvant therapy might be helpful in decreasing NET size also, leading us to the point where a tumour, previously considered inoperable, becomes operable. The aim of the study was to assess the usage of peptide receptor radionuclide therapy (PRRT) as a neoadjuvant treatment, enabling surgical intervention in primary inoperable NET.MethodsAmong 47 patients treated with PRRT, 6 patients were chosen with large, inoperable tumours, for whom enabling of complete surgical excision of the lesions might offer the prospect for a cure. Response to the therapy was assessed according to Response Evaluation Criteria In Solid Tumors (RECIST).ResultsThe mean tumour size decreased from 6.9 (min. 3.1 cm, max. 9.6 cm) before therapy to 5.4 cm (min. 3.1 cm, max. 9.5 cm) after the treatment. According to RECIST, stabilization of the disease was observed in four and partial responses in two patients. In two patients, reduction of the tumour size enabled surgical intervention.Conclusion(1) PRRT might be considered a neoadjuvant therapy in primary inoperable NETs. (2) According to RECIST, stabilization of the disease was observed in the majority of patients. (3) We suggest that not only tumour diameter changes, but also tumour volume and contrast enhancement changes in computed tomography should be taken into consideration in assessment of the response to the therapy. (4) Somatostatin receptor scintigraphy is an important tool for qualification of the radioisotope therapy and also for the assessment of the response to PRRT.

Magnetic resonance imaging dynamics of contrast medium uptake in vestibular schwannomas

Efficacy of radiosurgery in vestibular schwannoma (VS) is usually documented by changes of tumor size and by loss of contrast enhancement in MR imaging within the central portion of the lesion. Until now, however, correlation between contrast enhancement and timing of image acquisition in nontreated VS has not been analyzed systematically. The authors undertook this study to investigate changes in contrast enhancement with respect to latency of image acquisition after contrast agent administration. The dynamics of contrast medium uptake were evaluated with T1-weighted VIBE MR imaging sequences performed immediately and 1.5, 3.5, 4.5, 9.5, and 11.5 minutes after administration of single dose of Gd in 21 patients with nontreated medium- to large-sized VSs. Signal-to-noise (SNR) and contrast-to-noise ratio (CNR) of tumors were evaluated, and volumes of central nonenhancing areas (NEAs) were determined. The interior appearance of the tumors changed considerably over time. The NEA significantly diminished in size (p < 0.0001, Friedman test) and almost completely disappeared in all but 2 patients. Compared to images at 1.5 minutes, NEA volumes decreased to a median of 36% at 3.5 minutes and 34% at 4.5 minutes, showing smaller changes after that-9% at 9.5 minutes and 3% at 11.5 minutes. Tumor SNR and CNR increased over time. The maximum change in the median values for SNR and CNR were a 72% increase and 117% increase, respectively; both occurred at 1.5 minutes after Gd administration. Contrast enhancement in VS MR imaging varies according to the duration of the delay between contrast agent administration and image acquisition. Postradiotherapy changes in contrast enhancement of VS can therefore not be attributed only to effective radiotherapy. So-called "loss of central contrast enhancement" may be falsely detected because of timing. A standardized protocol with defined timing of image acquisition may increase comparability of contrast uptake in VS.

Ultrasonographic and Magnetic Resonance Imaging Findings of Testicular Lymphoma

Purpose : To evaluate the specific radiologic findings of testicular lymphoma which will be able to differentiated from other testicular tumors. Materials and Methods : Pathologically confirmed eight cases were included in this study. All eight cases were performed ultrasonography and four cases were performed magnetic resonance image. On ultrasonography, the size, location, shape, margin, internal echogenicity, homogeneity and vascularity were evaluated. On magnetic resonance image, the shape, margin, homogeneity, signal intensity on T1- and T2-weighted images, degree and homogeneity of the contrast enhancement and contrast enhancement change on dynamic enhancement study. Results : The margin of the mass was smooth on 6 of 8 patients. Internal echogenicity of the mass lesion was hypoechoic than normal testicular parenchyme on 7 of 8 patients. Four cases were homogeneous, 3 cases were relatively homogeneous and 1 case was heterogeneous. All 8 cases showed increased vascularity. The mass lesion was iso-signal intensity on T1-weighted image and low-signal intensity on T2-weighted image. All four cases were enhanced homogeneously and mildly than enhancing normal testicular parenchyme. On dynamic enhancement study, the mass lesion is progressively enhanced with time. Conclusion : The possibility of testicular lymphoma should be considered when testicular mass was homogeneously hypoechoic and low signal intensity on T2-weighted image in old age patients.

The Loss of Radiographic Enhancement in Primary Renal Cell Carcinoma Tumors Following Multitargeted Receptor Tyrosine Kinase Therapy is an Additional Indicator of Response

To characterize radiographic intratumoral contrast enhancement in the primary tumor of patients with renal cell carcinoma treated with either sorafenib or sunitinib, and to compare the relationship between primary tumor response and loss of enhancement. Use of the antiangiogenic multitargeted tyrosine kinase inhibitors sorafenib and sunitinib in renal cell carcinoma often results in stabilization of tumor size based on measurement of external tumor diameter; however, internal tumor changes in enhancement have been occasionally noted. Thirty patients who received sunitinib or sorafenib therapy were evaluated for primary tumor response with contrast-enhanced computed tomography images before and after at least 1 cycle of treatment. Evaluation of intratumoral contrast enhancement was quantified using a workstation that allowed for three-dimensional renderings of the kidney and measurement of density in Hounsfield units (HU). The relationship between loss of intratumoral enhancement and other outcome variables was examined. A loss of enhancement within the primary tumor, following therapy with tyrosine kinase inhibitors, was positively associated with primary tumor response (P = .0053). Additionally, the degree of post-treatment tumor enhancement was positively associated with tumor response to tyrosine kinase inhibition (P = .045). Intratumoral changes in computed tomography enhancement after receptor tyrosine kinase inhibition correlate with primary tumor response, and may be a useful adjunct to the standard response evaluation criteria in solid tumors (RECIST criteria) in assessing response to therapy. Prospective studies evaluating antiangiogenic agents should explore intratumoral changes in contrast enhancement as part of response criteria, and examine the effect of intratumoral changes on survival-based outcomes.