Perfusion Signal Research Articles

Optimization of adiabatic pulses for pulsed arterial spin labeling at 7 tesla: Comparison with pseudo-continuous arterial spin labeling.

To optimize and evaluate adiabatic pulses for pulsed arterial spin labeling at ultrahigh field 7 tesla. Four common adiabatic inversion pulses, including hyperbolic secant, wideband uniform rate smooth truncation, frequency offset corrected inversion, and time-resampled frequency offset corrected inversion pulses, were optimized based on a custom-defined loss function that included labeling efficiency and inversion band uniformity. The optimized pulses were implemented in flow-sensitive alternating inversion recovery sequences and tested on phantom and 11 healthy volunteers with 2 constraints: 1) specific absorption rate normalized; and 2) equal peak RF amplitude, respectively. A pseudo-continuous arterial spin labeling sequence was implemented for comparison. Quantitative metrics such as perfusion and relative labeling efficiency versus residual tissue signal were calculated. Among the 4 pulses, the wideband uniform rate smooth truncation pulse yielded the lowest loss in simulation and achieved a good balance between labeling efficiency and residual tissue signal from both phantom and in vivo experiments. Wideband uniform rate smooth truncation-pulsed arterial spin labeling showed significantly higher relative labeling efficiency compared to the other sequences (P < .01), whereas the perfusion signal was increased by 40% when the highest amplitude was used. The 4 pulsed arterial spin labeling sequences yielded comparable perfusion signals compared to pseudo-continuous arterial spin labeling but with less than half the specific absorption rate. Optimized wideband uniform rate smooth truncation pulse with the highest amplitude allowed was recommended for 7 tesla pulsed arterial spin labeling.

WARMING EFFECT OF BLANKETS WITH HIGH FAR-INFRARED EMISSIVITY ON SKIN MICROCIRCULATION IN TYPE 2 DIABETIC PATIENTS

Vascular complications are responsible for most of the morbidity and mortality in diabetic patients. Effective strategies to improve circulation appear to be another important issue in addition to the interventions of blood glucose control. Previous studies have shown that the biological effects on humans after using the materials containing ceramic particles emits far infrared radiation (FIR). The present study is to investigate the warming effect of the fabrics containing specified metals in diabetic patients. A total of 28 diabetic patients were blinded and randomly assigned to treatment group ([Formula: see text]) and control group ([Formula: see text]), respectively. The subjects of treatment group were ministered with the blankets with fibers containing the specified metals, while the subjects of control group were provided with blankets of ordinary material. The skin temperature and microcirculatory perfusion were monitored before and after 20-min use of the blankets at shoulder and bilateral calves. After warming with blankets, the treatment group revealed a higher increased ratio of skin perfusion than control ([Formula: see text]), while there was no prominent variation on the wavelet spectrum of the perfusion signal. Although it is already a known fact that passive FIR warming has the advantages of safety and convenience, our results suggest that warming by wearing the textiles containing the specified metals with high FIR emissivity is a solution for daily skin care of diabetic patients.

Assessment of myocardial viability using a minimally invasive laser Doppler flowmetry on pig model

The intra-operative real-time assessment of tissue viability can potentially improve therapy delivery and clinical outcome in cardiovascular therapies. Cardiac ablation therapy for the treatment of supraventricular or ventricular arrhythmia continues to be done without being able to assess if the intended lesion and lesion size have been achieved. Here, we report a method for continuous measurements of cardiac muscle microcirculation to provide an instrument for real-time ablation monitoring. We performed two acute open chest animal studies to assess the ability to perform real-time monitoring of creation and size of ablation lesion using a standard RF irrigated catheter. Radiofrequency ablation and laser Doppler were applied to different endocardial areas of alive open-chest pig. We performed two experiments at three different RF ablation energy setting and different ablation times. Perfusion signals before and after ablation were found extensively and distinctively different. By increasing the ablation energy and time, the perfusion signal was decreasing. In vivo assessing the local microcirculation during RF ablation by laser Doppler can potentially be useful to differentiate between viable and nonviable ablated beating heart in real time.

Contribution of perfusion to the 11 C-acetate signal in brown adipose tissue assessed by DCE-MRI and 68 Ga-DOTA PET in a rat model.

Determine if dynamic contrast enhanced (DCE) -MRI and/or 68 gallium 1,4,7,10-tetraazacyclododecane N, N', N″, N‴-tretraacetic acid (68 Ga-DOTA) positron emission tomography (PET) can assess perfusion in rat brown adipose tissue (BAT). Evaluate changes in perfusion between cold-stimulated and heat-inhibited BAT. Determine if the 11 C-acetate pharmacokinetic model can be constrained with perfusion information to improve assessment of BAT oxidative metabolism. Rats were split into three groups. In group 1 (N=6), DCE-MRI with gadobutrol was compared directly to 68 Ga-DOTA PET following exposure to 10°C for 48h. 11 C-Acetate PET was also performed to assess oxidation. In group 2 (N=4), only 68 Ga-DOTA PET was acquired following exposure to 10°C for 48h. Finally, in group 3 (N=10), perfusion was assessed with DCE-MRI in rats exposed to 10°C or 30°C for 48h, and oxidation was measured with 11 C-acetate. Perfusion was quantified with a two-compartment pharmacokinetic model, while oxidation was assessed by a four-compartment model. DCE-MRI and 68 Ga-DOTA PET provided similar perfusion measures, but a decrease in the perfusion signal was noted with longer imaging sessions. Exposure to 10°C or 30°C did not affect the perfusion measures, but the 11 C-acetate signal increased in BAT at 10°C. Without prior information about blood volume, the 11 C-acetate compartment model overestimated blood volume and underestimated oxidation in 10°C BAT. Precise assessment of oxidation via 11 C-acetate PET requires prior information about blood volume which can be obtained by DCE-MRI or 68 Ga-DOTA PET. Since perfusion can change rapidly, simultaneous PET-MRI would be preferred.

Fate of Patients with Chronic Cerebrovascular Steno-occlusive Disease According to Change of Cerebral Perfusion, Cerebrovascular Reserved, and Incidence of Recurrent Ischemic Stroke.

Objective:The objective is to demonstrate change of cerebral perfusion and cerebrovascular reserve (CVR) in treating patients with cerebrovascular steno-occlusive disease stratified by change of cerebral perfusion and CVR.Methods:Retrospective review patients with radiographic proven major cerebrovascular steno-occlusive disease whom underwent cerebral perfusion imaging with vasoactive stimuli stress test in Siriraj Hospital and Bangkok General Hospital during 2010–2018. Medical records were also reviewed. Radiographic findings, cerebral perfusion parameters and signal change during the stress test were reviewed and used to categorize into three groups.Results:There were 40 patients sent to radiology department for the evaluation of CVR. One patient had airway problem during the procedure and was excluded. Remaining 39 patients were included in this study (32 males and 7 females, mean age of 54.55 years). In 42 sites involved, 28 (66%) were internal carotid artery, 14 (33%) were middle cerebral arteries. Laterality is left side in 20 cases, right side in 14 cases, and bilateral in 5 cases. Poor CVR response (increased cerebral blood flow <10%) was found in 9 patients (2 severe stenoses and 7 total occlusions). The mean follow-up time was 28.9 months. Eight cases (20.5%) underwent surgical treatment; surgical bypasses and endovascular interventions. Only one patient had subsequential ischemic symptom at immediate postoperative vascular bypass surgery. The remaining patients had no report of progressive or recurrent neurological deficit symptom.Conclusion:Poor CVR response is more often found in higher degree of steno-occlusion. Even inconclusive predicting incidence of recurrent ischemic stroke, CVR that reflects the capacity of neuro-autoregulation.

Differential contribution of excitatory and inhibitory neurons in shaping neurovascular coupling in different epileptic neural states

Understanding the neurovascular coupling (NVC) underlying hemodynamic changes in epilepsy is crucial to properly interpreting functional brain imaging signals associated with epileptic events. However, how excitatory and inhibitory neurons affect vascular responses in different epileptic states remains unknown. We conducted real-time in vivo measurements of cerebral blood flow (CBF), vessel diameter, and excitatory and inhibitory neuronal calcium signals during recurrent focal seizures. During preictal states, decreases in CBF and arteriole diameter were closely related to decreased γ-band local field potential (LFP) power, which was linked to relatively elevated excitatory and reduced inhibitory neuronal activity levels. Notably, this preictal condition was followed by a strengthened ictal event. In particular, the preictal inhibitory activity level was positively correlated with coherent oscillating activity specific to inhibitory neurons. In contrast, ictal states were characterized by elevated synchrony in excitatory neurons. Given these findings, we suggest that excitatory and inhibitory neurons differentially contribute to shaping the ictal and preictal neural states, respectively. Moreover, the preictal vascular activity, alongside with the γ-band, may reflect the relative levels of excitatory and inhibitory neuronal activity, and upcoming ictal activity. Our findings provide useful insights into how perfusion signals of different epileptic states are related in terms of NVC.

Improved velocity‐selective‐inversion arterial spin labeling for cerebral blood flow mapping with 3D acquisition

To further optimize the velocity-selective arterial spin labeling (VSASL) sequence utilizing a Fourier-transform based velocity-selective inversion (FT-VSI) pulse train, and to evaluate its utility for 3D mapping of cerebral blood flow (CBF) with a gradient- and spin-echo (GRASE) readout. First, numerical simulations and phantom experiments were done to test the susceptibility to eddy currents and B1 field inhomogeneities for FT-VSI pulse trains with block and composite refocusing pulses. Second, the choices of the post-labeling delay (PLD) for FT-VSI prepared 3D VSASL were evaluated for the sensitivity to perfusion signal. The study was conducted among a young-age and a middle-age group at 3T. Both signal-to-noise ratio (SNR) and CBF were quantitatively compared with pseudo-continuous ASL (PCASL). The optimized 3D VSI-ASL was also qualitatively compared with PCASL in a whole-brain coverage among two healthy volunteers and a brain tumor patient. The simulations and phantom test showed that composite refocusing pulses are more robust to both eddy-currents and B1 field inhomogeneities than block pulses. 3D VSASL images with FT-VSI preparation were acquired over a range of PLDs and PLD = 1.2 s was selected for its higher perfusion signal. FT-VSI labeling produced quantitative CBF maps with 27% higher SNR in gray matter compared to PCASL. 3D whole-brain CBF mapping using VSI-ASL were comparable to the corresponding PCASL results. FT-VSI with 3D-GRASE readout was successfully implemented and showed higher sensitivity to perfusion signal than PCASL for both young and middle-aged healthy volunteers.

Measuring Knee Bone Marrow Perfusion Using Arterial Spin Labeling at 3\u2009T

Bone perfusion is an essential physiological measure reflecting vasculature status and tissue viability of the skeletal system. Arterial spin labeling (ASL), as a non-invasive and non-contrast enhanced perfusion imaging method, is an attractive approach for human research studies. To evaluate the feasibility of ASL perfusion imaging of knee bone marrow in the distal femoral condyle at a 3 T MRI scanner, a study was performed with eight healthy volunteers (three males and five females, 26 ± 2 years old) and two patients (male, 15 and 11 years old) with diagnosed stage II juvenile osteochondritis dissecans (JOCD). ASL imaging utilized a flow-sensitive alternating inversion recovery method for labeling and a single-shot fast spin echo sequence for image readout. In addition to quantitative knee bone marrow ASL imaging, studies were also performed to evaluate the effects of prolonged post-bolus delay and varied labeling size. ASL imaging was successfully performed with all volunteers. Despite the benefits of hyper-intensive signal suppression within bone marrow, the use of a prolonged post-bolus delay caused excessive perfusion signal decay, resulting in low perfusion signal-to-noise ratio (SNR) and poor image quality. Bone marrow perfusion signal changed with the labeling size, suggesting that the measured bone marrow perfusion signal is flow-associated. The means and standard deviations of bone marrow blood flow, spatial SNR, and temporal SNR from the quantitative perfusion study were 38.3 ± 5.2 mL/100 g/min, 3.31 ± 0.48, and 1.33 ± 0.31, respectively. The imaging results from JOCD patients demonstrated the potential of ASL imaging to detect disease-associated bone marrow perfusion changes. This study demonstrates that it is feasible to perform ASL imaging of knee bone marrow in the distal femoral condyle at 3 T.

Anoxic Brain Injury Detection with the Normalized Diffusion to ASL Perfusion Ratio: Implications for Blood-Brain Barrier Injury and Permeability.

Anoxic brain injury is a result of prolonged hypoxia. We sought to describe the nonquantitative arterial spin-labeling perfusion imaging patterns of anoxic brain injury, characterize the relationship of arterial spin-labeling and DWI, and evaluate the normalized diffusion-to-perfusion ratio to differentiate patients with anoxic brain injury from healthy controls. We identified all patients diagnosed with anoxic brain injuries from 2002 to 2019. Twelve ROIs were drawn on arterial spin-labeling with coordinate-matched ROIs identified on DWI. Linear regression analysis was performed to examine the relationship between arterial spin-labeling perfusion and diffusion signal. Normalized diffusion-to-perfusion maps were generated using a custom-built algorithm. Thirty-five patients with anoxic brain injuries and 34 healthy controls were identified. Linear regression analysis demonstrated a significant positive correlation between arterial spin-labeling and DWI signal. By means of a combinatory cutoff of slope of >0 and R2 of > 0.78, linear regression using arterial spin-labeling and DWI showed a sensitivity of 0.86 (95% CI, 0.71-0.94) and specificity of 0.82 (95% CI, 0.66-0.92) for anoxic brain injuries. A normalized diffusion-to-perfusion color map demonstrated heterogeneous ratios throughout the brain in healthy controls and homogeneous ratios in patients with anoxic brain injuries. In anoxic brain injuries, a homogeneously positive correlation between qualitative perfusion and DWI signal was identified so that areas of increased diffusion signal showed increased ASL signal. By exploiting this relationship, the normalized diffusion-to-perfusion ratio color map may be a valuable imaging biomarker for diagnosing anoxic brain injury and potentially assessing BBB integrity.

Systematic evaluation of velocity-selective arterial spin labeling settings for placental perfusion measurement.

PurposePlacental function is key for successful human pregnancies. Perfusion may be a sensitive marker for the in vivo assessment of placental function. Arterial spin labeling (ASL) MRI enables noninvasive measurement of tissue perfusion and it was recently suggested that ASL with velocity‐selective (VS) labeling could be advantageous in the placenta. We systematically evaluated essential VS‐ASL sequence parameters to determine optimal settings for efficient placental perfusion measurements.MethodsEleven pregnant women were scanned at 3T using VS‐ASL with 2D multislice echo planar imaging (EPI)‐readout. One reference VS‐ASL scan was acquired in all subjects; within subgroups the following parameters were systematically varied: cutoff velocity, velocity encoding direction, and inflow time. Visual evaluation and region of interest analyses were performed to compare perfusion signal differences between acquisitions.ResultsIn all subjects, a perfusion pattern with clear hyperintense focal regions was observed. Perfusion signal decreased with inflow time and cutoff velocity. Subject‐specific dependence on velocity encoding direction was observed. High temporal signal‐to‐noise ratios with high contrast on the perfusion images between the hyperintense regions and placental tissue were seen at ~1.6 cm/s cutoff velocity and ~1000 ms inflow time. Evaluation of measurements at multiple inflow times revealed differences in blood flow dynamics between placental regions.ConclusionPlacental perfusion measurements are feasible at 3T using VS‐ASL with 2D multislice EPI‐readout. A clear dependence of perfusion signal on VS labeling parameters and inflow time was demonstrated. Whereas multiple parameter combinations may advance the interpretation of placental circulation dynamics, this study provides a basis to select an effective set of parameters for the observation of placenta perfusion natural history and its potential pathological changes.

Invasive Assessment of the Myocardial Microcirculation during Beating Heart Coronary Artery Bypass Grafting.

Coronary artery bypass grafting may be associated with several cardiac complications, including ischemia, acute myocardial infarction, arrhythmias, or hemodynamic instability. Accumulating evidence suggests that well-developed coronary collateral circulation may protect against adverse effects, including myocardial ischemia. Assessment of myocardial microvascular perfusion is, therefore, of great clinical interest in beating heart surgery. In this paper, myocardial microvascular perfusion is continuously assessed on the beating heart using laser Doppler flowmetry in consecutive patients who underwent coronary artery bypass grafting procedures. No significant (p = 0.110) differences were found between the averaged perfusion signal (n = 42) at the baseline, during artery occlusion, or after reperfusion (732.4 ± 148.0 vs. 711.4 ± 144.1 vs. 737.0 ± 141.2, respectively). In contrast, significantly different (p < 0.001) mean perfusion signals (n = 12) were found (805.4 ± 200.1 vs. 577.2 ± 212.8 vs. 649.3 ± 220.8) in a subset of patients who presented with hemodynamic instability and myocardial ischemia. Additionally, a strong positive correlation between the plasma levels of high-sensitivity troponin I and perfusion decrease level after artery occlusion was found (r = 0.854, p < 0.001). This study argues that myocardial microvascular perfusion remains constant during coronary artery bypass grafting on the beating heart in advanced coronary artery disease. This phenomenon is most likely due to an extensive coronary collateral circulation.

Texture Analysis is a Useful Tool to Assess the Complexity Profile of Microcirculatory Blood Flow

The quantitative assessment of cardiovascular functions is particularly complicated, especially during any physiological challenge (e.g., exercise), with physiological signals showing intricate oscillatory properties. Signal complexity is one of such properties, and reflects the adaptability of the physiological systems that generated them. However, it is still underexplored in vascular physiology. In the present study, we calculate the complexity of photoplethysmography (PPG) signals and their frequency components obtained with the wavelet transform (WT), with two analytical tools—(i) texture analysis (TA) of WT scalograms, and (ii) multiscale entropy (MSE) analysis. PPG signals were collected from twelve healthy young subjects (26.0 ± 5.0 y.o.) during a unilateral leg lowering maneuver to evoke the venoarteriolar reflex (VAR) while lying supine, with the contralateral leg remaining stationary. Results showed that TA was able to detect a decrease in complexity, viewed as an increase in texture entropy (TE), of the PPG scalograms during VAR, similarly to MSE, suggesting that a decrease in the competence of vascular regulation mechanisms might be present during VAR. Nonetheless, TA showed lower sensitivity than MSE for low frequency spectral regions. TA seems to be a promising and straightforward analytical tool for the assessment of the complexity of PPG perfusion signals.

Cardiac microcirculation assessment of diabetic patients according to the presence of peripheral microangiopathy, by MRI myocardial perfusion

Coronary flow reserve (CFR), ratio of maximal myocardial blood flow (MBF) during pharmacologically induced coronary vasodilation to resting MBF, is an integrated measure of flow through both the large epicardial coronary arteries and the microcirculation. CFR has been proposed as an indirect parameter to evaluate the function of the coronary microcirculation, and its impairment is a strong predictor of cardiovascular mortality. Rubidium PET-computed tomography scanner, the gold standard method to evaluate CFR is not available in France. We aimed to assess cardiac microcirculation using MRI myocardial perfusion in diabetic patients. Using semi-quantitative analysis by MRI, we estimated CFR by the Myocardial Perfusion Reserve Index (MPRI), ratio between perfusion signal (maximal upslope) with adenosine stress and rest of myocardial segments in 27 diabetic patients without coronary artery disease perfectly phenotype for microangiopathy (eye, kidney, nerve). MPRI was analyzed according to the presence of extra cardiac microangiopathy. This technique is feasible with routine MRI protocols. Reproducibility was very good: 99 myocardial segments analyzed by 2 independent observers: MPRI 2.2 ± 0.76 vs. 2.24 ± 0.8; mean of differences: − 0.033 IC95% [−0.13; 0.07]. MPRI was lower in the group of diabetic patients with extra-cardiac microangiopathy ( n = 11) as compared to the group without ( n = 16): 2.01 ± 0.78 vs. 2.31 ± 0.7, P = 0.51, not statistically significant because of the modest number of patients. CFR was significantly altered in myocardial segments analyzed in diabetics with microangiopathy ( n = 150) as compared to myocardial segments from diabetics without microangiopathy ( n = 192): 1,99 ± 0.83 vs. 2.35 ± 0.98 P < 0.002. Semi quantitative analysis of CFR is feasible in a daily routine after stress MRI. Preliminary result in diabetic patients suggests a strong link between microangiopathy and a decrease in CFR.

Effect of warm environment on the skin blood flow response to food intake

Background and objective Warm exposure places high demands on thermoregulation mechanisms, which depend on the effectiveness of the microvascular function. The associations between the microcirculation and metabolism in warm environments have received little attention. The purpose of this study was to explore skin blood flow (SkBF) in response to food intake in a warm environment compared to control. Methods Thirty-two healthy, acclimated-to-warm-environment and physically active participants were recruited (20 females and 12 males). They participated in two sessions (warm environment: 31 °C and control: 20 °C, presented in randomized order). SkBF was measured before and after standardized food intake through the acquisition of perfusion signals by laser Doppler flowmetry (Periflux System 5000), following a local heating protocol. Results SkBF was affected by the environmental temperature, showing an increase in the warm environment compared to control (all p < .001). SkBF was significantly affected by food intake (all p < .007), being reduced after meals. In the men’s group, SkBF was reduced in both environmental temperatures after meals. In women, meals affected SkBF at 20 °C but not in the warm environment. Conclusion These results may indicate a competition between thermo- and glyco-regulation in a warm environment to the detriment of glucose homeostasis in women.

Different lasers reveal different skin microcirculatory flowmotion - data from the wavelet transform analysis of human hindlimb perfusion

Laser Doppler flowmetry (LDF) and reflection photoplethysmography (PPG) are standard technologies to access microcirculatory function in vivo. However, different light frequencies mean different interaction with tissues, such that LDF and PPG flowmotion curves might have distinct meanings, particularly during adaptative (homeostatic) processes. Therefore, we analyzed LDF and PPG perfusion signals obtained in response to opposite challenges. Young healthy volunteers, both sexes, were assigned to Group 1 (n = 29), submitted to a normalized Swedish massage procedure in one lower limb, increasing perfusion, or Group 2 (n = 14), submitted to a hyperoxia challenge test, decreasing perfusion. LDF (Periflux 5000) and PPG (PLUX-Biosignals) green light sensors applied distally on both lower limbs recorded perfusion changes for each experimental protocol. Both techniques detected the perfusion increase with massage, and the perfusion decrease with hyperoxia, in both limbs. Further analysis with the wavelet transform (WT) revealed better depth-related discriminative ability for PPG (more superficial, less blood sampling) compared with LDF in both challenges. Spectral amplitude profiles consistently demonstrated better sensitivity for LDF, especially regarding the lowest frequency components. Strong correlations between components were not found. Therefore, LDF and PPG flowmotion curves are not equivalent, a relevant finding to better study microcirculatory physiology.

The costs and benefits of estimating T1 of tissue alongside cerebral blood flow and arterial transit time in pseudo-continuous arterial spin labeling.

Multi‐post‐labeling‐delay pseudo‐continuous arterial spin labeling (multi‐PLD PCASL) allows for absolute quantification of the cerebral blood flow (CBF) as well as the arterial transit time (ATT). Estimating these perfusion parameters from multi‐PLD PCASL data is a non‐linear inverse problem, which is commonly tackled by fitting the single‐compartment model (SCM) for PCASL, with CBF and ATT as free parameters. The longitudinal relaxation time of tissue T 1t is an important parameter in this model, as it governs the decay of the perfusion signal entirely upon entry in the imaging voxel. Conventionally, T 1t is fixed to a population average. This approach can cause CBF quantification errors, as T 1t can vary significantly inter‐ and intra‐subject. This study compares the impact on CBF quantification, in terms of accuracy and precision, of either fixing T 1t, the conventional approach, or estimating it alongside CBF and ATT. It is shown that the conventional approach can cause a significant bias in CBF. Indeed, simulation experiments reveal that if T 1t is fixed to a value that is 10% off its true value, this may already result in a bias of 15% in CBF. On the other hand, as is shown by both simulation and real data experiments, estimating T 1t along with CBF and ATT results in a loss of CBF precision of the same order, even if the experiment design is optimized for the latter estimation problem. Simulation experiments suggest that an optimal balance between accuracy and precision of CBF estimation from multi‐PLD PCASL data can be expected when using the two‐parameter estimator with a fixed T 1t value between population averages of T 1t and the longitudinal relaxation time of blood T 1b.

INNV-16. COMPLETE RESPONSE OF THALAMIC IDH WILDTYPE GLIOBLASTOMA AFTER PROTON THERAPY FOLLOWED BY CHEMOTHERAPY TOGETHER WITH TUMOR TREATING FIELDS

Abstract BACKGROUND Proton therapy is able to apply high radiation doses to the tumor while sparing healthy tissues by reducing integral dose. Tumor Treating Fields (TTFields) are low intensity (1–3 V/cm) and intermediate frequency (100–300 kHz) alternating electric fields that demonstrated significantly increased survival rates in combination with adjuvant temozolomide (TMZ) in patients with newly diagnosed glioblastoma (ndGBM). Here, we report on a patient with biopsied ndGBM IDH wildtype with complete radiological response. MATERIAL AND METHODS Brain MRI demonstrated an occlusive hydrocephalus and a ring enhancing lesion in the right posterior thalamus in a 42 year old male. After endoscopic ventriculostomy and stereotactic biopsy histopathological examination resulted in the diagnosis of a glioblastoma (WHO grade IV), IDH 1 wildtype (R132), IDH 2 wildtype (R172), HIST1H3B/C wildtype, TERT wildtype (C228 and C250), BRAF wildtype, and unmethylated MGMT promotor. The patient received definitive chemoradiation with TMZ to a total dose of 60Gy incl. proton boost of 5x2 GyRBE. TTFields therapy in combination with TMZ was initiated 4 weeks after completion of chemoradiation, TMZ maintenance was completed per protocol after 6 cycles. TTFields therapy was continued for more than 13 month and to-date the patient is still on therapy. RESULTS Current follow up time is 20 months after initial diagnosis with the patient showing a radiological complete response. In a MRI 9 months after proton therapy, partial response and perfusion restriction in the tumor area was observed. Another MRI 3 months later showed a complete response without perfusion signal in the tumor area. CONCLUSION Complete response was observed following combination treatment of chemoradiation with TMZ including proton boost, TMZ maintenance and TTFields in a patient with pathologically confirmed GBM IDH wildtype. To our knowledge, this is the first report on a ndGBM patient receiving proton therapy followed by TTFields therapy.

Intravascular signal suppression and microvascular signal mapping using delays alternating with nutation for tailored excitation (DANTE) pulse for arterial spin labeling perfusion imaging.

To optimize the delays alternating with nutation for tailored excitation (DANTE) pulse as a vascular crushing gradient to eliminate macro-and micro-vascular signals and to generate a macrovascular space-related map by applying DANTE with multiple conditions. Numerical simulation was performed to estimate the optimal flip angle (FA) of the DANTE. A phantom study was conducted to evaluate the impact of the FA and gradient area (GA) of the DANTE with three flow velocities and various parameters of the DANTE. Finally, an in vivo study was performed to assess the optimal DANTE parameters and to map the estimated macrovascular signal of the arterial spin labeling (ASL) signal. Numerical simulation revealed that the decrease of magnetization plateaued at 12.5° of FA. The phantom study showed that the setting of larger FA or GA decreased the ASL signals. The decrease of the ASL signal depended on the flow velocity, and the dependence increased with decreasing GA. The in vivo study revealed that larger FA and GA decreased the perfusion signal. An optimized DANTE makes it possible to efficiently suppress the macro-and-micro vascular signals depending on the flow velocity. Moreover, macrovascular signal mapping may be useful to assess altered hemodynamic states.

P14.07 Complete response under treatment with proton therapy followed by chemotherapy together with Tumor Treating Fields in a biopsied IDH wildtype glioblastoma patient

Abstract BACKGROUND Proton therapy is able to apply high radiation doses to the tumor while sparing healthy tissues by reducing integral dose. Tumor Treating Fields (TTFields) are low intensity (1–3 V/cm) and intermediate frequency (100–300 kHz) alternating electric fields that demonstrated significantly increased survival rates in combination with adjuvant temozolomide (TMZ) in patients with newly diagnosed glioblastoma (ndGBM). Especially in ndGBM IDH wildtype with unmethylated MGMT promotor therapeutic options are restricted. Here, we report on a patient with biopsied ndGBM IDH wildtype with complete radiological response. MATERIAL AND METHODS Brain MRI demonstrated an occlusive hydrocephalus and a ring enhancing lesion in the right posterior thalamus in a 42 year old male. Endoscopic third ventriculostomy and stereotactic biopsy of the lesion were performed. Histopathological examination resulted in the diagnosis of a glioblastoma (WHO grade IV), IDH 1 wildtype (R132), IDH 2 wildtype (R172), HIST1H3B/C wildtype, TERT wildtype (C228 and C250), BRAF wildtype, and unmethylated MGMT promotor. In view of the tumor site, resection was not feasible. Consequently, the patient received definitive chemoradiation with TMZ to a total dose of 60Gy incl. proton boost of 5x2 GyRBE. TTFields therapy in combination with TMZ was initiated 4 weeks after completion of chemoradiation, TMZ maintenance was completed per protocol after 6 cycles. TTFields therapy was continued for more than 13 month and to-date the patient is still on therapy. RESULTS Current follow up time is 20 months after initial diagnosis with the patient showing a radiological complete response. The first MRI following chemoradiation with TMZ and protons (showed pseudoprogression. After 3 months, the MRI again showed slightly increasing contrast enhancement. However, no clinical symptoms of tumor progression were present. The TTFields usage (compliance) rate, i.e. the rate per time the patient is applying the therapy, of the patient was 86 %. This was well above the independent prognostic threshold of 75 % and supports the feasibility of this approach. A further MRI after 8 weeks showed a stable disease. In a MRI 4 months later, partial response with decreased contrast enhancement plus perfusion restriction in the tumor area was observed. Another MRI after 3 months showed a complete response without perfusion signal in the tumor area. In the clinical examination the patient had no neurological deficits and to-date the patient is still stable CONCLUSION Complete response was observed following combination treatment of chemoradiation with TMZ including proton boost, TMZ maintenance and TTFields in a patient with pathologically confirmed GBM IDH wildtype. To our knowledge, this is the first report on a ndGBM patient receiving proton therapy followed by TTFields therapy.

Preoperative Magnetic Resonance Imaging Based Predictive Modeling of Brain Tumor Laser Ablation

Abstract INTRODUCTION Laser interstitial thermal therapy (LITT) yields precise lesions under magnetic resonance imaging (MRI) thermometry guidance and is revolutionizing brain tumor management. However, one limitation is the inability to preoperatively predict how tumors will respond to thermal energy. Our study assessed whether preoperative variables correlated with intraoperative LITT ablation dynamics were capable of predicting how ablations progressed. METHODS Pixels indicating irreversible damage were quantified as a function of time for 101 brain tumor patients treated with LITT. Ablation dynamics were determined using pixel counts modeled with first-order dynamics and related to independent preoperative variables using stepwise regression. The resulting models were evaluated for predictive accuracy using leave-one-out cross-validation analysis. RESULTS Total pixels ablated is larger for LITT performed at a high laser power and for a long duration and for lesions with a low T1 GAD signal. The rate of pixel increase is elevated with high laser power and for lesions with a low T2 signal and prior radiotherapy. Pixel counts are well modeled with first-order dynamics. Scale factor (C) is positively related to perfusion, laser power, and T2 signal and negatively related to T1 signal. Time constant (t) is positively related to T2 signal and perfusion. Tshift is negatively related to T2 signal and laser power. Pathology did not impact ablation dynamics, although the presence of radiation necrosis resulted in faster and larger ablations. A predictive model based on the independent variables accounts for 77% of the variance in ablation pixel counts. CONCLUSION Preoperative MRI features correlate with brain tumor LITT ablation dynamics. Predictive models based on these features may eventually be used to guide the planning and delivery of LITT.