TY  - JOUR
A1  - Pennig, Lenhard
A1  - Hoyer, Ulrike Cornelia Isabel
A1  - Krauskopf, Alexandra
A1  - Shahzad, Rahil
A1  - Jünger, Stephanie T.
A1  - Thiele, Frank
A1  - Laukamp, Kai Roman
A1  - Grunz, Jan-Peter
A1  - Perkuhn, Michael
A1  - Schlamann, Marc
A1  - Kabbasch, Christoph
A1  - Borggrefe, Jan
A1  - Goertz, Lukas
T1  - Deep learning assistance increases the detection sensitivity of radiologists for secondary intracranial aneurysms in subarachnoid hemorrhage
JF  - Neuroradiology
N2  - Purpose
To evaluate whether a deep learning model (DLM) could increase the detection sensitivity of radiologists for intracranial aneurysms on CT angiography (CTA) in aneurysmal subarachnoid hemorrhage (aSAH).

Methods
Three different DLMs were trained on CTA datasets of 68 aSAH patients with 79 aneurysms with their outputs being combined applying ensemble learning (DLM-Ens). The DLM-Ens was evaluated on an independent test set of 104 aSAH patients with 126 aneuryms (mean volume 129.2 ± 185.4 mm3, 13.0% at the posterior circulation), which were determined by two radiologists and one neurosurgeon in consensus using CTA and digital subtraction angiography scans. CTA scans of the test set were then presented to three blinded radiologists (reader 1: 13, reader 2: 4, and reader 3: 3 years of experience in diagnostic neuroradiology), who assessed them individually for aneurysms. Detection sensitivities for aneurysms of the readers with and without the assistance of the DLM were compared.

Results
In the test set, the detection sensitivity of the DLM-Ens (85.7%) was comparable to the radiologists (reader 1: 91.2%, reader 2: 86.5%, and reader 3: 86.5%; Fleiss κ of 0.502). DLM-assistance significantly increased the detection sensitivity (reader 1: 97.6%, reader 2: 97.6%,and reader 3: 96.0%; overall P=.024; Fleiss κ of 0.878), especially for secondary aneurysms (88.2% of the additional aneurysms provided by the DLM).

Conclusion
Deep learning significantly improved the detection sensitivity of radiologists for aneurysms in aSAH, especially for secondary aneurysms. It therefore represents a valuable adjunct for physicians to establish an accurate diagnosis in order to optimize patient treatment.
KW  - aneurysms
KW  - aneurysmal subarachnoid hemorrhage
KW  - CT angiography
KW  - deep learning
KW  - convolutional neural networks
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-308117
SN  - 0028-3940
SN  - 1432-1920
VL  - 63
IS  - 12
ER  - 
TY  - JOUR
A1  - Hoyer, Jan
A1  - Schatzschneider, Ulrich
A1  - Schulz-Siegmund, Michaela
A1  - Neundorf, Ines
T1  - Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery
JF  - Beilstein Journal of Organic Chemistry
N2  - Over the past 20 years, cell-penetrating peptides (CPPs) have gained tremendous interest due to their ability to deliver a variety of therapeutically active molecules that would otherwise be unable to cross the cellular membrane due to their size or hydrophilicity. Recently, we reported on the identification of a novel CPP, sC18, which is derived from the C-terminus of the 18 kDa cationic antimicrobial protein. Furthermore, we demonstrated successful application of sC18 for the delivery of functionalized cyclopentadienyl manganese tricarbonyl (cymantrene) complexes to tumor cell lines, inducing high cellular toxicity. In order to increase the potential of the organometallic complexes to kill tumor cells, we were looking for a way to enhance cellular uptake. Therefore, we designed a branched dimeric variant of sC18, (sC18)\(_2\), which was shown to have a dramatically improved capacity to internalize into various cell lines, even primary cells, using flow cytometry and fluorescence microscopy. Cell viability assays indicated increased cytotoxicity of the dimer presumably caused by membrane leakage; however, this effect turned out to be dependent on the specific cell type. Finally, we could show that conjugation of a functionalized cymantrene with (sC18)\(_2\) leads to significant reduction of its IC\(_{50}\) value in tumor cells compared to the respective sC18 conjugate, proving that dimerization is a useful method to increase the drug-delivery potential of a cell-penetrating peptide.
KW  - peptides
KW  - internalization studies
KW  - drug delivery
KW  - cell-penetrating peptides
KW  - anti-tumor agents
KW  - organometallic complexes
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-133933
VL  - 8
ER  -