Using DWI-MRI parameters from multi- B values acquisition and a histogram approach for assessment of early therapeutic response in glioblastoma

Abstract Early evaluation of therapeutic response of GBM on imaging is limited by poor biological specificity of clinical MRI. Clinical DWI-MRI models assume diffusion is mono-exponential when derived from only two B-values, although it has been proven diffusion is multiexponential. Purpose: To assess the utility of quantitative diffusion MRI derived from multi B-value acquisitions in the assessment of treatment response. Methods: 13 patients were enrolled into our multicentre study. Imaging was performed pre-RT and mid-RT using a multi B-value acquisition. Histograms within ROIs defined by abnormal FLAIR signal. Changes in histogram percentile profiles were evaluated across the two timepoints and compared with RANO assessment. Results: Following treatment, 5 patients had PD, 4 SD and 4 CR. Patients with PD showed a histogram shift to the left across all models, in keeping with increased cellularity. Parameters DDC and f are the most predictive of PD against RANO assessment, and appear superior to ADC. Reduction in 75th centile (f) and 95th centile (DDC) are the most sensitive histogram metrics for predicting early PD. Discussion: This is the first study to use histogram analysis as a marker of early treatment response in GBM. Results suggest association between early changes in specific diffusion components and subsequent treatment response. Spatially-independent diffusion parameter comparisons provide unbiased sampling of tumour heterogeneity. Conclusion: Our preliminary data suggest differential changes in diffusion parameters early in treatment, and provide proof of principle for multi B-value analysis and spatially-independent longitudinal assessment of diffusion imaging for therapeutic assessment in GBM.

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NIMG-55. TO ASSESS THE UTILITY OF ADVANCED QUANTITATIVE DIFFUSION MRI DERIVED FROM MULTI B VALUE ACQUISITIONS IN THE ASSESSMENT OF TREATMENT RESPONSE, USING A SPATIALLY-INDEPENDENT APPROACH

Neuro-Oncology ◽

10.1093/neuonc/noz175.724 ◽

2019 ◽

Vol 21 (Supplement_6) ◽

pp. vi173-vi173

Author(s):

Shah Islam ◽

Melanie Morrison ◽

Adam Waldman

Keyword(s):

Treatment Response ◽

Diffusion Mri ◽

Tumour Growth ◽

Progressive Disease ◽

B Value ◽

Subsequent Treatment ◽

Tumour Heterogeneity ◽

High B Value ◽

Mri Protocol ◽

Early Progressive Disease

Abstract PURPOSE To assess the utility of advanced diffusion MRI derived from multi b value acquisitions in the assessment of treatment response, using a spatially-independent approach. METHOD AND MATERIALS 13 GBM patients were enrolled into our multicentre study. All patients completed RT with TMZ. Imaging was performed pre-RT and mid RT. The MRI protocol included a ‘low’ b value acquisition (b= 0s/mm, 50s/mm, 150s/mm, 200s/mm, 500s/mm, 1000s/mm) from which monoexponential diffusion indices ADC and biexponential indices, IVIM parameters D*, D and f were calculated. A ‘high b value’ acquisition (b=0 s/mm, 500s/mm, 1000s/mm, 1500s/mm, 2000s/mm, 2500s/mm, 3000s/mm, 3500s/mm, 4000s/mm) was acquired to allow stretched exponential diffusion indices, DDC and alpha to be derived. FLAIR sequences were used to define ROI and clinical assessment of mid-treatment and end-treatment response using RANO criteria. Histograms were generated from voxels located within manually segmented ROIs defined by increased signal on T2 FLAIR images. Changes in histogram percentile profiles were evaluated across the two timepoints and compared with RANO assessment at the mid treatment and end treatment timepoints. RESULTS Following completion of treatment, 5 patients had PD, 4 SD and 4 CR. Patients with PD showed a histogram shift to the left across all diffusion models, in keeping with increasing diffusion restriction and implying increased cellularity. Patients with SD or CR showed little or no shift in the histogram. DDC and f are the most predictive of progression against RANO assessment, and appear superior to routine ADC. Reduction in 75th centile (f) and 95th centile (DDC) are the most sensitive histogram metrics for predicting early progressive disease. CONCLUSION Results suggest association between early changes in specific diffusion components and subsequent treatment response. Spatially-independent diffusion parameter comparisons provide unbiased sampling of tumour heterogeneity and abrogate the confound of voxel-to-voxel misregistration due to tumour growth/shrinkage.

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Signal to noise and b-value analysis for optimal intra-voxel incoherent motion imaging in the brain

PLoS ONE ◽

10.1371/journal.pone.0257545 ◽

2021 ◽

Vol 16 (9) ◽

pp. e0257545

Author(s):

Harri Merisaari ◽

Christian Federau

Keyword(s):

B Value ◽

Quantitative Information ◽

Physiological Noise ◽

Value Analysis ◽

B Values ◽

High B Value ◽

Noise Characteristics ◽

Acquisition Scheme ◽

The Brain

Intravoxel incoherent motion (IVIM) is a method that can provide quantitative information about perfusion in the human body, in vivo, and without contrast agent. Unfortunately, the IVIM perfusion parameter maps are known to be relatively noisy in the brain, in particular for the pseudo-diffusion coefficient, which might hinder its potential broader use in clinical applications. Therefore, we studied the conditions to produce optimal IVIM perfusion images in the brain. IVIM imaging was performed on a 3-Tesla clinical system in four healthy volunteers, with 16 b values 0, 10, 20, 40, 80, 110, 140, 170, 200, 300, 400, 500, 600, 700, 800, 900 s/mm2, repeated 20 times. We analyzed the noise characteristics of the trace images as a function of b-value, and the homogeneity of the IVIM parameter maps across number of averages and sub-sets of the acquired b values. We found two peaks of noise of the trace images as function of b value, one due to thermal noise at high b-value, and one due to physiological noise at low b-value. The selection of b value distribution was found to have higher impact on the homogeneity of the IVIM parameter maps than the number of averages. Based on evaluations, we suggest an optimal b value acquisition scheme for a 12 min scan as 0 (7), 20 (4), 140 (19), 300 (9), 500 (19), 700 (1), 800 (4), 900 (1) s/mm2.

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MESMERISED: Super-accelerated 7 T STEAM imaging for quantitative multi-contrast and diffusion MRI

10.1101/2020.05.15.098269 ◽

2020 ◽

Author(s):

F.J. Fritz ◽

B.A. Poser ◽

A. Roebroeck

Keyword(s):

Diffusion Mri ◽

Diffusion Tensor ◽

Diffusion Imaging ◽

B Value ◽

Diffusion Kurtosis Imaging ◽

Acquisition Time ◽

Whole Brain ◽

B Values ◽

Isotropic Resolution ◽

And Diffusion

AbstractThere is an increasing interest in quantitative imaging of T1, T2 and diffusion contrast in the brain due to greater robustness against bias fields and artifacts, as well as better biophysical interpretability in terms of microstructure. However, acquisition time constraints are a challenge, particularly when multiple quantitative contrasts are desired and when extensive sampling of diffusion directions, high b-values or long diffusion times are needed for multi-compartment microstructure modeling. Although ultra-high fields of 7 T and above have desirable properties for many MR modalities, the shortening T2 and the high specific absorption rate (SAR) of inversion and refocusing pulses bring great challenges to quantitative T1, T2 and diffusion imaging. Here, we present the MESMERISED sequence (Multiplexed Echo Shifted Multiband Excited and Recalled Imaging of STEAM Encoded Diffusion). MESMERISED removes the dead time in Stimulated Echo Acquisition Mode (STEAM) imaging by an echo-shifting mechanism. The echo-shift (ES) factor is independent of multiband (MB) acceleration and allows for very high multiplicative (ESxMB) acceleration factors, particularly under moderate and long mixing times. This results in high duty cycle and time efficiency at 7 T, particularly for quantitative T1 and diffusion imaging, while also retaining the capacity to perform quantitative T2 and B1 mapping. We demonstrate the super-acceleration of MESMERISED for whole-brain T1 relaxometry with total acceleration factors up to 36 at 1.8 mm isotropic resolution, and up to 54 at 1.25 mm resolution qT1 imaging, corresponding to a 6x and 9x speed-up, respectively, compared to MB-only accelerated acquisitions. We demonstrate quantitative T2 and B1 mapping to illustrate multi-contrast mapping with the same MESMERISED sequence and the same readout train. Finally, we demonstrate highly efficient diffusion MRI with high b-values and long diffusion times in two separate cases. First, we show that super-accelerated multi-shell diffusion acquisitions with 370 whole-brain diffusion volumes over 8 b-value shells up to b = 7000 s/mm2 can be generated at 2 mm isotropic in under 8 minutes, a data rate of almost a volume per second, or at 1.8 mm isotropic in under 11 minutes. Second, we demonstrate time-efficient sampling of different diffusion times with 1.8 mm isotropic diffusion data acquired at four diffusion times up to 290 ms, which supports both Diffusion Tensor Imaging (DTI) and Diffusion Kurtosis Imaging (DKI) at each diffusion time. MESMERISED extends possibilities to efficiently probe T1, T2 and diffusion contrast for multi-component modeling of tissue microstructure.

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[68Ga]Ga-PSMA-HBED-CC PET/CT demonstrates to be superior to ceCT in detecting early treatment response in metastatic clear cell renal cell carcinoma

European Journal of Nuclear Medicine and Molecular Imaging ◽

10.1007/s00259-021-05250-1 ◽

2021 ◽

Author(s):

Priscilla Guglielmo ◽

Donatello Gasparro ◽

Maura Scarlattei ◽

Giorgio Baldari ◽

Stefano Bola ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Cell Carcinoma ◽

Treatment Response ◽

Early Treatment ◽

Renal Cell ◽

Clear Cell ◽

Cell Renal Cell Carcinoma ◽

Early Treatment Response ◽

Pet Ct

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Diverse metabolic response of cancer cells treated with a 213Bi-anti-EGFR-immunoconjugate

Scientific Reports ◽

10.1038/s41598-021-84421-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Benedikt Feuerecker ◽

Philipp Biechl ◽

Christof Seidl ◽

Frank Bruchertseifer ◽

Alfred Morgenstern ◽

...

Keyword(s):

Amino Acids ◽

Cancer Cells ◽

Treatment Response ◽

Cell Lines ◽

Egf Receptor ◽

Metabolic Response ◽

Gas Chromatography Mass Spectrometry ◽

Alpha Emitter ◽

Early Treatment Response ◽

Bladder Cancer Cells

AbstractEvaluation of treatment response is among the major challenges in modern oncology. We herein used a monoclonal antibody targeting the EGF receptor (EGFR) labelled with the alpha emitter 213Bi (213Bi-anti-EGFR-MAb). EJ28Luc (bladder) and LN18 (glioma) cancer cells, both overexpressing EGFR, were incubated for 3 h with the radioimmunoconjugate. To assess the responses in the core carbon metabolism upon this treatment, these cancer cell lines were subsequently cultivated for 18 h in the presence of [U-13C6]glucose. 13C-enrichment and isotopologue profiles of key amino acids were monitored by gas chromatography–mass spectrometry (GC/MS), in order to monitor the impacts of the radionuclide-treatment upon glucose metabolism. In comparison to untreated controls, treatment of EJ28Luc cells with 213Bi-anti-EGFR-MAb resulted in a significantly decreased incorporation of 13C from [U-13C6]glucose into alanine, aspartate, glutamate, glycine, proline and serine. In sharp contrast, the same amino acids did not display less 13C-enrichments during treatment of the LN18 cells. The data indicate early treatment response of the bladder cancer cells, but not of the glioma cells though cell lines were killed following 213Bi-anti-EGFR-MAb treatment. The pilot study shows that the 13C-labelling approach is a valid tool to assess the responsiveness of cancer cells upon radionuclide-treatment in considerable metabolic detail.

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Early Treatment Outcomes for Bloodstream Infections Caused by Potential AmpC Beta-lactamase-producing Enterobacterales with Focus on Piperacillin/Tazobactam: A Retrospective Cohort Study

Antibiotics ◽

10.3390/antibiotics10060665 ◽

2021 ◽

Vol 10 (6) ◽

pp. 665

Author(s):

Lena Herrmann ◽

Aurelia Kimmig ◽

Jürgen Rödel ◽

Stefan Hagel ◽

Norman Rose ◽

...

Keyword(s):

Cohort Study ◽

Treatment Outcomes ◽

Treatment Response ◽

Sofa Score ◽

Early Treatment ◽

Primary Outcome ◽

Bloodstream Infections ◽

Beta Lactamase ◽

Early Treatment Response

The Gram-negative bacilli Serratia spp., Providencia spp., Morganella morganii, Citrobacter freundii complex, Enterobacter spp. and Klebsiella aerogenes are common Enterobacterales that may harbor inducible chromosomal AmpC beta-lactamase genes. The purpose of the present study was to evaluate treatment outcomes and identify predictors of early treatment response in patients with bloodstream infection caused by potential AmpC beta-lactamase-producing Enterobacterales (SPICE-BSI). This cohort study included adult patients with SPICE-BSI hospitalized between 01/2011 and 02/2019. The primary outcome was early treatment response 72 h after the start of active treatment, defined as survival, hemodynamic stability, improved or stable SOFA score, resolution of fever and leukocytosis and microbiologic resolution. Among 295 included patients, the most common focus was the lower respiratory tract (27.8%), and Enterobacter spp. (n = 155) was the main pathogen. The early treatment response rate was significantly lower (p = 0.006) in the piperacillin/tazobactam group (17/81 patients, 21.0%) than in the carbapenem group (40/82 patients, 48.8%). Independent negative predictors of early treatment response (p < 0.02) included initial SOFA score, liver comorbidity and empiric piperacillin/tazobactam treatment. In vitro piperacillin/tazobactam resistance was detected in three patients with relapsed Enterobacter-BSI and initial treatment with piperacillin/tazobactam. In conclusion, our findings show that piperacillin/tazobactam might be associated with early treatment failure in patients with SPICE-BSI.

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