Cell tracking technologies for acute ischemic brain injury

Stem cell therapy has showed considerable potential in the treatment of stroke over the last decade. In order that these therapies may be optimized, the relative benefits of growth factor release, immunomodulation, and direct tissue replacement by therapeutic stem cells are widely under investigation. Fundamental to the progress of this research are effective imaging techniques that enable cell tracking in vivo. Direct analysis of the benefit of cell therapy includes the study of cell migration, localization, division and/or differentiation, and survival. This review explores the various imaging tools currently used in clinics and laboratories, addressing image resolution, long-term cell monitoring, imaging agents/isotopes, as well as safety and costs associated with each technique. Finally, burgeoning tracking techniques are discussed, with emphasis on multimodal imaging.     

Evaluation of microwave ablation of liver malignancy with enabled constant spatial energy control to achieve a predictable spherical ablation zone

Objectives: To evaluate the clinical performance of a new microwave ablation (MWA) system with enabled constant spatial energy control (ECSEC) to achieve spherical ablation zones in the treatment of liver malignancies.

Materials and methods: In this retrospective study, 56 hepatic tumours in 48 patients (23 men, 25 women; mean age: 59.6 years) were treated using a new high-frequency MWA-system with ECSEC. Parameters evaluated were technical success, technical efficacy, tumour diameter, tumour and ablation volume, complication rate, 90-day mortality, local tumour progression (LTP) at the 12-month follow-up, ablative margin and ablation zone sphericity. These parameters were compared using the Kruskal–Wallis test with the same parameters collected retrospectively from cohorts of patients treated with conventional high-frequency (HF) MWA (n?=?20) or low-frequency (LF) MWA (n?=?20).

Results: Technical success was achieved in all interventions. The technical efficacy was 100% (ECSEC) vs. 100% (LF-MWA) vs. 95% (HF-MWA). There were no intra-procedural deaths or major complications. Minor complications occurred in 3.57% (2/56), 0% (0/20) and 0% (0/20) of the patients, respectively. The one-year mortality rate was 16.1% (9/56), 15% (3/20) and 10% (2/20), respectively. The LTP was 3.57% (2/56), 5% (1/20) and 5% (1/20), respectively. The median deviation from ideal sphericity (1.0) was 0.135 (ECSEC) vs. 0.344 (LF-MWA) vs. 0.314 (HF-MWA) (p?p?Conclusions: Microwave ablation of liver malignancies is a safe and efficient treatment independent of the system used. Hepatic MWA with ECSEC achieves significantly more spherical ablation zones and higher minimal ablative margins.     

Intraprocedural blood volume measurement using C-arm CT as a predictor for treatment response of malignant liver tumours undergoing repetitive transarterial chemoembolization (TACE)

Purpose

To evaluate feasibility of measuring parenchymal blood volume (PBV) of malignant hepatic tumours using C-arm CT, test the changes in PBV following repeated transarterial chemoembolization (TACE) and correlate these changes with the change in tumour size in MRI.

Methods

111 patients with liver malignancy were included. Patients underwent MRI and TACE in a 4- to 6-week interval. During intervention C-arm CT was performed. Images were post-processed to generate PBV maps. Blood volume data in C-arm CT and change in size in MRI were evaluated. The correlation between PBV and size was tested using Spearman rank test.

Results

Pre-interventional PBV maps showed a mean blood volume of 84.5 ml/1000 ml?±?62.0, follow-up PBV maps after multiple TACE demonstrated 61.1 ml/1000 ml?±?57.5. The change in PBV was statistically significant (p?=?0.02). Patients with initial tumour blood volume >100 ml/1000 ml dropped 7.1 % in size and 47.2 % in blood volume; 50–100 ml/1000 ml dropped 4.6 % in size and 25.7 % in blood volume; and <50 ml/1000 ml decreased 2.8 % in size and increased 82.2 % in blood volume.

Conclusion

PBV measurement of malignant liver tumours using C-arm CT is feasible. Following TACE PBV decreased significantly. Patients with low initial PBV show low local response rates and further increase in blood volume, whereas high initial tumour PBV showed better response to TACE.

Key Points

? Parenchymal blood volume assessment of malignant hepatic lesions using C-arm CT is feasible. ? The parenchymal blood volume is reduced significantly following transarterial chemoembolization. ? Parenchymal blood volume can monitor the response of tumours after transarterial chemoembolization. ? Although not significant, high initial parenchymal blood volume yields better response to TACE.

     

MR angiography-planned prostatic artery embolization for benign prostatic hyperplasia: single-center retrospective study in 56 patients

PURPOSEWe aimed to evaluate the advantages of magnetic resonance angiography (MRA)-planned prostatic artery embolization (PAE) for benign prostatic hyperplasia (BPH).METHODSIn this retrospective study, MRAs of 56 patients (mean age, 67.23±7.73 years; age range, 47–82 years) who underwent PAE between 2017 and 2018 were evaluated. For inclusion, full information about procedure time and radiation values must have been available. To identify prostatic artery (PA) origin, three-dimensional MRA reconstruction with maximum intensity projection was conducted in every patient. In total, 33 patients completed clinical and imaging follow-up and were included in clinical evaluation.RESULTSThere were 131 PAs with a second PA in 19 pelvic sides. PA origin was correctly identified via MRA in 108 of 131 PAs (82.44%). In patients in which MRA allowed a PA analysis, a significant reduction of the fluoroscopy time (−27.0%, p = 0.028) and of the dose area product (−38.0%, p = 0.003) was detected versus those with no PA analysis prior to PAE. Intervention time was reduced by 13.2%, (p = 0.25). Mean fluoroscopy time was 30.1 min, mean dose area product 27,749 μGy·m², and mean entrance dose 1553 mGy. Technical success was achieved in all 56 patients (100.0%); all patients were embolized on both pelvic sides. The evaluated data documented a significant reduction in international prostate symptom scores (p < 0.001; mean 9.67 points).CONCLUSIONMRA prior to PAE allowed the identification of PA in 82.44% of the cases. MRA-planned PAE is an effective treatment for patients with BPH.

A profound knowledge about pelvic vessel anatomy is essential for achieving successful prostatic artery embolization (PAE), to improve the safety of PAE and to avoid major complications as non-target embolization (1–6). This knowledge can be achieved by using angiographic techniques to show pelvic artery anatomy, although the best method is still controversially discussed. In some studies, computed tomography (CT) angiography (CTA) was used for pre-interventional evaluation as it is described to have high certainty in analyzing prostatic artery (PA) anatomy (1, 3, 7). Other institutes use digital subtraction angiography (DSA) and cone beam CT (CBCT) for analysis without any pre-procedural vessel imaging (8–11). Since peri-interventional DSA findings may be ambiguous and CTA or CBCT would imply additional radiation, magnetic resonance angiography (MRA) seems to be a promising method to analyze PA origin without radiation. However, Maclean et al. (3) recommend CT for planning PAE instead of magnetic resonance imaging (MRI) as the latter is more expensive and more time-consuming. Pisco et al. (5, 12) state that MRA does not have enough resolution for clear identification of PA origin and does not provide the same information as CTA.Currently only a few studies discuss the suitability of MRA for preprocedural planning of PAE. Kim et al. (13) first investigated this subject with a sample size of 17 patients and documented an accuracy of 76.5% for PA origin analysis. However, in this study no clinical evaluation was included. Zhang et al. (4) investigated MRA analysis prior to PAE in a randomized clinical trial with 100 patients. A sensitivity of 91.5% and a significant reduction of procedure time, fluoroscopy time, radiation dose, and contrast medium volume due to pre-interventional MRA were documented. In his review, Prince (14) agrees with Zhang et al. (4) that MRA may be a suitable method for planning PAE.Because of the skeptical comments whether performing MRA prior to PAE is practical on a daily basis in a radiological institution, an assessment of these parameters in a less selective nature was necessary. In addition, contrary to Zhang et al. (4) who used MIP-reconstructions and 5° interval images for their assessment, we used a three-dimensional (3D) reconstruction of the pelvic arterial tree based on the MRA sequences. The main advantage of the 3D reconstruction is that it can be freely rotated in all directions which allowed an easy identification and tracking of the PA.In this study, the advantages and clinical outcome of pre-interventional analysis of PA via MRA as a possible radiation-free planning method and its influence on procedure time and radiation dose were investigated.     

VJ REARRANGEMENTS OF THE TCRγ LOCUS IN PERIPHERAL T-CELL LYMPHOMAS: ANALYSIS BY POLYMERASE CHAIN REACTION AND DENATURING GRADIENT GEL ELECTROPHORESIS

Using Southern blotting for the diagnosis of clonality in peripheral T-cell lymphomas (PTCLs), analysis of the T-cell receptor (TCR) γ gene rearrangement was shown to be more informative than that of the TCR β gene rearrangement. In order to amplify every VJγ rearrangement, a polymerase chain reaction (PCR) procedure using newly designed GC-clamp primers has been developed. All primers can be mixed in a single multiplex PCR. PCR products are analysed by denaturing gradient gel electrophoresis (DGGE), providing tumour-specific imprints inasmuch as the procedure characterizes N sequence polymorphism at the VJ junctions. In a series of 30 PTCL cases, the PCR procedure demonstrated 27 cases to be clonally rearranged and failed in three cases. PCR was more accurate than Southern blotting, showing 47 rearranged γ alleles, four of which were undetectable on the Southern blot. When lymphomas were studied at different sites and at relapse, the DGGE pattern remained unchanged. In PTCL, the proposed PCR is helpful for the diagnosis and staging of the disease and should improve the follow-up monitoring. The undetectability of clonal rearrangements in a few cases is discussed in the light of concepts of lymphomagenesis and T-cell differentiation.     

Initial experience with repetitive transarterial chemoembolization (TACE) as a third line treatment of ovarian cancer metastasis to the liver: indications, outcomes and role in patient's management

Objective

To evaluate local tumor control and survival data after transarterial chemoembolization (TACE) with different drug combinations in the palliative third-line treatment of patients with ovarian cancer liver metastases.

Methods

Sixty-five patients (mean age: 51.5 year) with unresectable hematogenous hepatic metastases of ovarian cancer who did not respond to systemic chemotherapy were repeatedly treated with TACE in 4-week intervals. The local chemotherapy protocol consisted of Mitomycin (group 1) (n = 14; 21.5%), Mitomycin with Gemcitabine (group 2) (n = 26; 40%), or Mitomycin with Gemcitabine and Cisplatin (group 3) (n = 25; 38.5%). Embolization was performed with Lipiodol and starch microspheres. Local tumor response was evaluated by MRI according to RECIST criteria. Survival data were calculated according to the Kaplan-Meier method.

Results

The local tumor control was: partial response (PR) in 16.9% (n = 11), stable disease (SD) in 58.5% (n = 38) and progressive disease (PD) in 24.6% (n = 16) of patients. In group 1, we observed SD in 78.6% (11/14), and PD in 21.4% (3/14) of patients. In group 2, PR in 7.7% (2/26), SD in 57.7% (15/26), and PD in 34.6% (9/26) of patients. In group 3, PR in 36% (9/25), SD in 48% (12/25), and PD in 16% (4/25) of patients. Survival rate from the start of TACE was 58% after 1-year, 19% after 2-years, and 13% after 3-years. The median and mean survival times were 14 and 18.5 months without statistically significant difference for the 3 groups of patients (p = 0.502).

Conclusion

Transarterial chemoembolization is effective palliative treatment in achieving local control in selected patients with liver metastases from ovarian cancer.     

Repetitive transarterial chemoembolization (TACE) of liver metastases from gastric cancer: Local control and survival results

Objective

To evaluate the local tumor control and survival data after transarterial chemoembolization with different drug combinations in the palliative treatment of patients with liver metastases of gastric cancer.

Materials and methods

The study was retrospectively performed. 56 patients (mean age, 52.4) with unresectable liver metastases of gastric cancer who did not respond to systemic chemotherapy were repeatedly treated with TACE in 4-week intervals. In total, 310 chemoembolization procedures were performed (mean, 5.5 sessions per patient). The local chemotherapy protocol consisted of mitomycin alone (30.4%), mitomycin and gemcitabine (33.9%), or mitomycin, gemcitabine and cisplatin (35.7%). Embolization was performed with lipiodol and starch microspheres. Local tumor response was evaluated by MRI according to RECIST. Survival data from first chemoembolization were calculated according to the Kaplan–Meier method.

Results

The local tumor control was: complete response in 1.8% (n = 1), partial response in 1.8% (n = 1), stable disease in 51.8% (n = 29) and progressive disease in 44.6% (n = 25) of patients. The 1-, 2-, and 3-year survival rate from the start of chemoembolization were 58%, 38%, and 23% respectively. The median and mean survival times were 13 and 27.1 months. A Statistically significant difference between patients treated with different chemotherapy protocols was noted (ρ = 0.045) with the best survival time in the mitomycin, gemcitabine and cisplatin group.

Conclusion

Transarterial chemoembolization is a minimally invasive therapy option for palliative treatment of liver metastases in patients with gastric cancer.     

Neoadjuvant TACE before laser induced thermotherapy (LITT) in the treatment of non-colorectal non-breast cancer liver metastases: Feasibility and survival rates

Purpose

To evaluate safety, feasibility and overall survival rates for transarterial chemoembolization (TACE) alone or combined with MR-guided laser-induced-thermotherapy (LITT) in liver metastases of non-colorectal and non-breast cancer origin.

Methods and materials

Included were patients with unresectable non-colorectal non-breast cancer liver metastases with progression under systemic chemotherapy. Excluded were patients with Karnofsky score ≤70, respiratory, renal and cardiovascular failure, and general TACE contraindications. TACE using Mitomycin alone, Mitomycin–Gemcitabine or Mitomycin–Gemcitabine–Cisplatin was performed to all patients. After TACE 146 metastases were ablated with MR-guided LITT. To be eligible for LITT metastases should be <5 cm in size and ≤5 in number. Tumor response was evaluated using MRI according to RECIST. Survival was evaluated using Kaplan–Meier analysis.

Results

A total of 110 patients (mean age 59.2 years) with 371 metastases received TACE (mean 5.4 sessions/patient, n = 110) with 76 (69%) receiving LITT (mean 1.6 session/patient) afterwards. TACE resulted in a mean decrease of mean maximum diameter of 52% ± 26.6 and volume change of −68.5% ± 22.9 in the 25 patients (23%) with partial response. Stable disease (n = 59, 54%). Progressive disease (n = 26, 23%). The RECIST outcome after LITT showed complete response (n = 13, 17%), partial response (n = 1, 1%), stable situation (n = 41, 54%) and progressive disease (n = 21, 28%). The mean time to progression (TTP) was 8.6 months. Median survival of all patients was 21.1 months.

Conclusion

TACE with different protocols alone and in combination with LITT is a feasible palliative treatment option resulting in a median survival of 21.1 months for unresectable liver metastases of non-colorectal and non-breast cancer origin.