RESUMEN

BACKGROUND: Gliomas are highly invasive brain neoplasms. MRI is the most important tool to diagnose and monitor glioma but has shortcomings. In particular, the assessment of tumor cell invasion is insufficient. This is a clinical dilemma, as recurrence can arise from MRI-occult glioma cell invasion. HYPOTHESIS: Tumor cell invasion, tumor growth and radiotherapy alter the brain parenchymal microstructure and thus are assessable by diffusion tensor imaging (DTI) and MR elastography (MRE). STUDY TYPE: Experimental, animal model. ANIMAL MODEL: Twenty-three male NMRI nude mice orthotopically implanted with S24 patient-derived glioma cells (experimental mice) and 9 NMRI nude mice stereotactically injected with 1 µL PBS (sham-injected mice). FIELD STRENGTH/SEQUENCE: 2D and 3D T2-weighted rapid acquisition with refocused echoes (RARE), 2D echo planar imaging (EPI) DTI, 2D multi-slice multi-echo (MSME) T2 relaxometry, 3D MSME MRE at 900 Hz acquired at 9.4 T (675 mT/m gradient strength). ASSESSMENT: Longitudinal 4-weekly imaging was performed for up to 4 months. Tumor volume was assessed in experimental mice (n = 10 treatment-control, n = 13 radiotherapy). The radiotherapy subgroup and 5 sham-injected mice underwent irradiation (3 × 6 Gy) 9 weeks post-implantation/sham injection. MRI-/MRE-parameters were assessed in the corpus callosum and tumor core/injection tract. Imaging data were correlated to light sheet microscopy (LSM) and histology. STATISTICAL TESTS: Paired and unpaired t-tests, a P-value ≤0.05 was considered significant. RESULTS: From week 4 to 8, a significant callosal stiffening (4.44 ± 0.22 vs. 5.31 ± 0.29 kPa) was detected correlating with LSM-proven tumor cell invasion. This was occult to all other imaging metrics. Histologically proven tissue destruction in the tumor core led to an increased T2 relaxation time (41.65 ± 0.34 vs. 44.83 ± 0.66 msec) and ADC (610.2 ± 12.27 vs. 711.2 ± 13.42 × 10-6 mm2/s) and a softening (5.51 ± 0.30 vs. 4.24 ± 0.29 kPa) from week 8 to 12. Radiotherapy slowed tumor progression. DATA CONCLUSION: MRE is promising for the assessment of key glioma characteristics. EVIDENCE LEVEL: NA TECHNICAL EFFICACY: Stage 2.

RESUMEN

Glioblastoma is the most common and aggressive primary malignant brain tumor with poor prognosis. Novel immunotherapeutic approaches are currently under investigation. Even though magnetic resonance imaging (MRI) is the most important imaging tool for treatment monitoring, response assessment is often hampered by therapy-related tissue changes. As tumor and therapy-associated tissue reactions differ structurally, we hypothesize that biomechanics could be a pertinent imaging proxy for differentiation. Longitudinal MRI and magnetic resonance elastography (MRE) were performed to monitor response to immunotherapy with a toll-like receptor 7/8 agonist in orthotopic syngeneic experimental glioma. Imaging results were correlated to histology and light sheet microscopy data. Here, we identify MRE as a promising non-invasive imaging method for immunotherapy-monitoring by quantifying changes in response-related tumor mechanics. Specifically, we show that a relative softening of treated compared to untreated tumors is linked to the inflammatory processes following therapy-induced re-education of tumor-associated myeloid cells. Mechanistically, combined effects of myeloid influx and inflammation including extracellular matrix degradation following immunotherapy form the basis of treated tumors being softer than untreated glioma. This is a very early indicator of therapy response outperforming established imaging metrics such as tumor volume. The overall anti-tumor inflammatory processes likely have similar effects on human brain tissue biomechanics, making MRE a promising tool for gauging response to immunotherapy in glioma patients early, thereby strongly impacting patient pathway.

Asunto(s)

RESUMEN

The optimum therapy of a torn PCL in multiligamental-injured knees is controversially discussed in literature. As conservative treatment and PCL reconstruction alone mostly lead to long-term immobilization, we performed a single stage PCL bracing with ACL reconstruction using ACL TightRopes® and Fiber-/TigerTapes® to accelerate back-to-sport after multiligamental knee injury with bicrucial tears. The brace consisted of two FiberTapes which were looped in an ACL TightRope and transosseously fixed with a Dog Bone-Button®. The ACL reconstruction was performed by a fourfolded semitendinosus graft in TightRope® technique. We chose an active rehabilitation-protocol with immediately allowed knee flexion to 90° in an ACL brace. This led to excellent results with resumption of sports after 6 months and good subjective and objective knee stability measured with a KT-1000. Our results hint that our method of bracing a torn PCL in multiligamental knee injuries may lead to faster rehabilitation with comparable knee stability.

RESUMEN

Objective: To compare short-, mid-, and long-term follow-up ablation zone volume alterations as well as imaging features on contrast-enhanced computed tomography (CT) after irreversible electroporation (IRE) of primary and secondary liver tumors with findings subsequent to radiofrequency ablation (RFA). Materials and Methods: Volume assessment of 39 ablation zones (19 RFA, 20 IRE) after intervention was performed at four time intervals (day 0 [t1; n = 39], day 1-7 [t2; n = 25], day 8-55 [t3; n = 28], after day 55 [t4; n = 23]) on dual-phase CT. Analysis of peripheral rim enhancement was conducted. Lesion's volume decrease relative to the volume at t1 was calculated and statistically analyzed with respect to patient's sex, age, ablation modality (IRE/RFA), and history of platinum-based chemotherapy (PCT). Results: No influence of patient's sex or age on ablation volume was detected. The decrease in ablation zones' volume was significantly larger (p < 0.05 for all time intervals) after IRE (arterial phase, 7.5%; venous phase, 9.7% of initial volume) compared to RFA (arterial phase, 39.6%; venous phase, 45.3% of initial volume). After RFA, significantly smaller decreases in the ablation volumes, in general, were detected in patients treated with PCT in their history (p = 0.004), which was not detected after IRE (p = 0.288). In the arterial phase, peripheral rim enhancement was frequently detected after both IRE and RFA. In the venous phase, rim-enhancement was depicted significantly more often following IRE at t1 and t2 (pt1 = 0.003, pt2 < 0.001). Conclusion: As per our analysis, ablation zone volume decreased significantly in a more rapid and more profound manner after IRE. Lesion's remodeling after RFA but not IRE seems to be influenced by PCT, possibly due to the type of cell death induced by the different ablation modalities.

Asunto(s)