Combining diffusion and perfusion differentiates tumor from bevacizumab-related imaging abnormality (bria).

A subset of patients with high-grade glioma and brain metastases who are treated with bevacizumab develop regions of marked and persistent restricted diffusion that do not reflect recurrent tumor. Here, we quantify the degree of restricted diffusion and the relative cerebral blood volume (rCBV) within these regions of bevacizumab-related imaging abnormality (BRIA) in order to facilitate differentiation of these lesions from recurrent tumor. Six patients with high-grade glioma and two patients with brain metastases who developed regions of restricted diffusion after initiation of bevacizumab were included. Six pre-treatment GBM controls were also included. Restriction spectrum imaging (RSI) was used to create diffusion maps which were co-registered with rCBV maps. Within regions of restricted diffusion, mean RSI values and mean rCBV values were calculated for patients with BRIA and for the GBM controls. These values were also calculated for normal-appearing white matter (NAWM). RSI values in regions of restricted diffusion were higher for both BRIA and tumor when compared to NAWM; furthermore RSI values in BRIA were slightly higher than in tumor. Conversely, rCBV values were very low in BRIA-lower than both tumor and NAWM. However, there was only a trend for rCBV values to be higher in tumor than in NAWM. When evaluating areas of restricted diffusion in patients with high-grade glioma or brain metastases treated with bevacizumab, RSI is better able to detect the presence of pathology whereas rCBV is better able to differentiate BRIA from tumor. Thus, combining these tools may help to differentiate necrotic tissue related to bevacizumab treatment from recurrent tumor.

Assessment of irradiated brain metastases using dynamic contrast-enhanced magnetic resonance imaging.

INTRODUCTION: The purpose of this study was to evaluate the effect of stereotactic radiosurgery (SRS) on cerebral metastases using the transfer constant (K trans) assessed by dynamic contrast-enhanced (DCE) MRI. Furthermore, we aimed to evaluate the ability of K trans measurements to predict midterm tumor outcomes after SRS. METHODS: The study received institutional review board approval, and informed consent was obtained from all subjects. Twenty-six adult patients with a total of 34 cerebral metastases underwent T1-weighted DCE MRI in a 1.5-T magnet at baseline (prior to SRS) and 4-8 weeks after treatment. Quantitative analysis of DCE MRI was performed by generating K trans parametric maps, and region-of-interest-based measurements were acquired for each metastasis. Conventional MRI was performed at least 16 weeks after SRS to assess midterm tumor outcome using volume variation. RESULTS: The mean (±SD) K trans value was 0.13 ± 0.11 min(-1) at baseline and 0.08 ± 0.07 min(-1) after 4-8 weeks post-treatment (p < 0.001). The mean (±SD) total follow-up time was 7.9 ± 4.7 months. Seventeen patients (22 lesions) underwent midterm MRI. Of those, nine (41 %) lesions had progressed at the midterm follow-up. An increase in K trans after SRS was predictive of tumor progression (hazard ratio = 1.50; 95 % CI = 1.16-1.70, p < 0.001). An increase of 15 % in K trans showed a sensitivity of 78 % and a specificity of 85 % for the prediction of progression at midterm follow-up. CONCLUSION: SRS was associated with a reduction of K trans values of the cerebral metastases in the early post-treatment period. Furthermore, K trans variation as assessed using DCE MRI may be helpful to predict midterm outcomes after SRS.

Vulnerability of Tritia reticulata (L.) early life stages to ocean acidification and warming.

Ocean acidification and warming (OA-W) result mainly from the absorption of carbon dioxide and heat by the oceans, altering its physical and chemical properties and affecting carbonate secretion by marine calcifiers such as gastropods. These processes are ongoing, and the projections of their aggravation are not encouraging. This work assesses the concomitant effect of the predicted pH decrease and temperature rise on early life stages of the neogastropod Tritia reticulata (L.), a common scavenger of high ecological importance on coastal ecosystems of the NE Atlantic. Veligers were exposed for 14 days to 12 OA-W experimental scenarios generated by a factorial design of three pH levels (targeting 8.1, 7.8 and 7.5) at four temperatures (16, 18, 20 and 22 °C). Results reveal effects of both pH and temperature (T °C) on larval development, growth, shell integrity and survival, individually or interactively at different exposure times. All endpoints were initially driven by pH, with impaired development and high mortalities being recorded in the first week, constrained by the most acidic scenarios (pHtarget 7.5). Development was also significantly driven by T °C, and its acceleration with warming was observed for the remaining exposure time. Still, by the end of this 2-weeks trial, larval performance and survival were highly affected by the interaction between pH and T °C: growth under warming was evident but only for T °C ≤ 20 °C and carbonate saturation (pHtarget ≥ 7.8). In fact, carbonate undersaturation rendered critical larval mortality (100%) at 22 °C, and the occurrence of extremely vulnerable, unshelled specimens in all other tested temperatures. As recruitment cohorts are the foundation for future populations, our results point towards the extreme vulnerability of this species in case tested scenarios become effective that, according to the IPCC, are projected for the northern hemisphere, where this species is ubiquitous, by the end of the century. Increased veliger mortality associated with reduced growth rates, shell dissolution and loss under OA-W projected scenarios will reduce larval performance, jeopardizing T. reticulata subsistence.

Restriction-Spectrum Imaging of Bevacizumab-Related Necrosis in a Patient with GBM.

IMPORTANCE: With the increasing use of antiangiogenic agents in the treatment of high-grade gliomas, we are becoming increasingly aware of distinctive imaging findings seen in a subset of patients treated with these agents. Of particular interest is the development of regions of marked and persistent restricted diffusion. We describe a case with histopathologic validation, confirming that this region of restricted diffusion represents necrosis and not viable tumor. OBSERVATIONS: We present a case report of a 52-year-old man with GBM treated with temozolomide, radiation, and concurrent bevacizumab following gross total resection. The patient underwent sequential MRI's which included restriction-spectrum imaging (RSI), an advanced diffusion-weighted imaging (DWI) technique, and MR perfusion. Following surgery, the patient developed an area of restricted diffusion on RSI which became larger and more confluent over the next several months. Marked signal intensity on RSI and very low cerebral blood volume (CBV) on MR perfusion led us to favor bevacizumab-related necrosis over recurrent tumor. Subsequent histopathologic evaluation confirmed coagulative necrosis. CONCLUSION AND RELEVANCE: Our report increases the number of pathologically proven cases of bevacizumab-related necrosis in the literature from three to four. Furthermore, our case demonstrates this phenomenon on RSI, which has been shown to have good sensitivity to restricted diffusion.

Glaucomatous optic nerve head alterations in patients with chronic heart failure.

PURPOSE: To evaluate the association between chronic heart failure (CHF) and optic nerve head alterations. METHODS: A cross-sectional study was performed. Heart failure patients with recent echocardiograms were subjected to ophthalmologic examinations, including intraocular pressure measurement, optic nerve head, and retinal nerve fiber layer evaluation using stereophotography, Heidelberg retinal tomography, and standard automated perimetry. The ocular findings were correlated with the cardiological evaluation, and compared with a control group without cardiopathy. RESULTS: A total of 30 patients with CHF and 30 individuals without cardiopathy were enrolled in this study. The mean (standard deviation [SD]) intraocular pressure was 12.3 (2.5) mmHg in the CHF group, and 14.7 (2.9) mmHg in the control group (P < 0.001). The mean (SD) arterial blood pressure was 86.9 (17.1) mmHg in the CHF group, and 103.6 (15.2) mmHg in the control group (P < 0.001). The mean (SD) ocular perfusion pressure was 45.6 (11.1) mmHg in the CHF group, and 54.4 (10.4) mmHg in the control group (P = 0.001). The mean (SD) rim area was 1.41 (0.3) mm(2) in the CHF group, and 1.60 (0.26) mm(2) in the control group (P = 0.003). The mean (SD) vertical cup/disc ratio was 0.51 (0.17) in the CHF group, and 0.41 (0.18) in the control group (P = 0.02). The Moorfields regression analysis was outside the normal limits in 16 out of 58 (27.6%) eyes of the CHF subjects, and in 4 out of 60 (6.7%) eyes of the control subjects (P = 0.01). The frequency of glaucoma was 10% in the CHF group, whereas none of the control subjects met the criteria for the diagnosis of glaucoma (P = 0.24). CONCLUSION: CHF is associated with lower ocular perfusion pressure, and glaucomatous optic nerve head changes.

Color Doppler imaging of the ophthalmic artery in patients with chronic heart failure.

PURPOSE: To evaluate the ophthalmic artery hemodynamics in patients with chronic heart failure. METHODS: Doppler parameters of ophthalmic artery of 18 patients with chronic heart failure in different stages of the disease were compared with 21 healthy volunteers (control group). These parameters were also correlated with echocardiographic assessments and clinical cardiologic status. RESULTS: Mean diastolic velocity was 5.14 ± 2.4 cm/s in the chronic heart failure group and 7.44 ± 3.5 cm/s in the control group (p=0.007). Mean resistance index of the ophthalmic artery was 0.76 ± 0.08 in the chronic heart failure group and 0.70 ± 0.08 in the control group (p=0.04). Mean systolic velocity of the ophthalmic artery was 22.03 ± 7.7 cm/s in the chronic heart failure group and 25.32 ± 9.2 cm/s in the control group (p=0.24). There was a negative correlation between the resistance index of the ophthalmic artery and systemic blood pressure of patients with chronic heart failure (r= -0.47, p=0.007). Diastolic velocity of the ophthalmic artery correlated positively with systemic blood pressure (r=0.44, p=0.02). CONCLUSION: Lower diastolic velocity and higher resistance index were observed in the ophthalmic artery of chronic heart failure patients when compared to the control group, which probably reflects the presence of orbital vasoconstriction in response to low cardiac output. Therefore, the influence of these findings on the structure and function of the optic nerve head deserves investigation.

Color Doppler imaging of the ophthalmic artery in patients with chronic heart failure / Ultrassonografia Doppler em cores da artéria oftálmica em pacientes com insuficiência cardíaca crônica

Purpose: To evaluate the ophthalmic artery hemodynamics in patients with chronic heart failure. Methods: Doppler parameters of ophthalmic artery of 18 patients with chronic heart failure in different stages of the disease were compared with 21 healthy volunteers (control group). These parameters were also correlated with echocardiographic assessments and clinical cardiologic status. Results: Mean diastolic velocity was 5.14 ± 2.4 cm/s in the chronic heart failure group and 7.44 ± 3.5 cm/s in the control group (p=0.007). Mean resistance index of the ophthalmic artery was 0.76 ± 0.08 in the chronic heart failure group and 0.70 ± 0.08 in the control group (p=0.04). Mean systolic velocity of the ophthalmic artery was 22.03 ± 7.7 cm/s in the chronic heart failure group and 25.32 ± 9.2 cm/s in the control group (p=0.24). There was a negative correlation between the resistance index of the ophthalmic artery and systemic blood pressure of patients with chronic heart failure (r= -0.47, p=0.007). Diastolic velocity of the ophthalmic artery correlated positively with systemic blood pressure (r=0.44, p=0.02). Conclusion: Lower diastolic velocity and higher resistance index were observed in the ophthalmic artery of chronic heart failure patients when compared to the control group, which probably reflects the presence of orbital vasoconstriction in response to low cardiac output. Therefore, the influence of these findings on the structure and function of the optic nerve head deserves investigation.

Objetivo: Avaliar o fluxo sanguíneo da artéria oftálmica em pacientes com insuficiência cardíaca crônica. Métodos: Parâmetros da ultrassonografia Doppler em cores da artéria oftálmica de 18 pacientes com insuficiência cardíaca crônica em diferentes estágios da doença foram comparados com 21 voluntários saudáveis (grupo controle). Estes parâmetros foram também correlacionados com avaliação ecocardiográfica e quadro clínico cardiológico. Resultados: A média da velocidade diastólica foi 5,14 ± 2,4 cm/s no grupo insuficiência cardíaca crônica e 7,44 ± 3,5 cm/s no grupo controle (p=0,007). O índice de resistência da artéria oftálmica foi de 0,76 ± 0,08 no grupo insuficiência cardíaca crônica e 0,70 ± 0,08 no grupo controle (p=0,04). A média de velocidade sistólica da artéria oftálmica foi 22,03 ± 7,7 cm/s no grupo insuficiência cardíaca crônica e 25,32 ± 9,2 cm/s no grupo controle (p=0,24). A pressão arterial sistêmica dos pacientes com insuficiência cardíaca crônica correlacionou-se negativamente com o índice de resistência da artéria oftálmica (r= -0,47, p=0,007) e positivamente com a velocidade diastólica da artéria oftálmica (r=0,44, p=0,02). Conclusão: Velocidade diastólica mais baixa e índice de resistência mais alto foram observados na artéria oftálmica de pacientes com insuficiência cardíaca crônica quando comparados ao grupo controle, o que provavelmente reflete a presença de vasoconstrição orbital em resposta ao baixo débito cardíaco. Portanto, a influência desses achados sobre a estrutura e função da cabeça do nervo óptico merece ser investigada.