Noncanonical effector functions of the T-memory-like T-PLL cell are shaped by cooperative TCL1A and TCR signaling.

T-cell prolymphocytic leukemia (T-PLL) is a poor-prognostic neoplasm. Differentiation stage and immune-effector functions of the underlying tumor cell are insufficiently characterized. Constitutive activation of the T-cell leukemia 1A (TCL1A) oncogene distinguishes the (pre)leukemic cell from regular postthymic T cells. We assessed activation-response patterns of the T-PLL lymphocyte and interrogated the modulatory impact by TCL1A. Immunophenotypic and gene expression profiles revealed a unique spectrum of memory-type differentiation of T-PLL with predominant central-memory stages and frequent noncanonical patterns. Virtually all T-PLL expressed a T-cell receptor (TCR) and/or CD28-coreceptor without overrepresentation of specific TCR clonotypes. The highly activated leukemic cells also revealed losses of negative-regulatory TCR coreceptors (eg, CTLA4). TCR stimulation of T-PLL cells evoked higher-than-normal cell-cycle transition and profiles of cytokine release that resembled those of normal memory T cells. More activated phenotypes and higher TCL1A correlated with inferior clinical outcomes. TCL1A was linked to the marked resistance of T-PLL to activation- and FAS-induced cell death. Enforced TCL1A enhanced phospho-activation of TCR kinases, second-messenger generation, and JAK/STAT or NFAT transcriptional responses. This reduced the input thresholds for IL-2 secretion in a sensitizer-like fashion. Mice of TCL1A-initiated protracted T-PLL development resembled such features. When equipped with epitope-defined TCRs or chimeric antigen receptors, these Lckpr-hTCL1Atg T cells gained a leukemogenic growth advantage in scenarios of receptor stimulation. Overall, we propose a model of T-PLL pathogenesis in which TCL1A enhances TCR signals and drives the accumulation of death-resistant memory-type cells that use amplified low-level stimulatory input, and whose loss of negative coregulators additionally maintains their activated state. Treatment rationales are provided by combined interception in TCR and survival signaling.

Virtual monoenergetic images from spectral detector computed tomography facilitate washout assessment in arterially hyper-enhancing liver lesions.

OBJECTIVES: To investigate whether the increased soft tissue contrast of virtual monoenergetic images (VMIs) obtained from a spectral detector computed tomography (SDCT) system improves washout assessment of arterially hyper-enhancing liver lesions. METHODS: Fifty-nine arterially hyper-enhancing lesions in 31 patients (age 65 ± 9 years, M/W 20/11) were included in this IRB-approved study. All patients underwent multi-phase SDCT for HCC screening. MRI, CEUS or biopsy within 3 months served as standard of reference to classify lesions as LiRADS 3 or 4/5. VMIs and conventional images (CIs) were reconstructed. Visual analysis was performed on 40, 60, and 80 kiloelectronvolt (keV) and CIs by 3 radiologists. Presence and visibility of washout were assessed; image quality and confidence of washout evaluation were evaluated on 5-point Likert scales. Signal-to-noise ratio (SNR), lesion-to-liver contrast-to-noise ratio (CNR) (|HUlesion-HUliver|/SDliver) and washout (|HUlesion-HUliver|) were calculated. Statistical assessment was performed using ANOVA and Wilcoxon test. RESULTS: On subjective lesion analysis, the highest level of diagnostic confidence and highest sensitivity for the detection of lesion washout were found for 40-keV VMIs (40 keV vs. CI, 81.3 vs. 71.3%). Image quality parameters were significantly better in low-kiloelectronvolt VMIs than in CIs (p < 0.05; e.g. SNRliver: 40 keV vs. CIs, 12.5 ± 4.1 vs. 5.6 ± 1.6). In LiRADS 4/5 lesions, CNR and quantitative washout values were significantly higher in 40-keV VMIs compared to CIs (p < 0.05; e.g. CNR and washout in 40 keV vs. CIs, 2.3 ± 1.6 vs. 0.8 ± 0.5 and 29.0 ± 19.1 vs. 12.9 ± 6.9 HU, respectively). CONCLUSION: By increasing lesion contrast, low-kiloelectronvolt VMIs obtained from SDCT improve washout assessment of hyper-enhancing liver lesions with respect to washout visibility and diagnostic confidence. KEY POINTS: • Low-kiloelectronvolt virtual monoenergetic images from spectral detector CT facilitate washout assessment in arterially hyper-enhancing liver lesions. • Image quality and quantitative washout parameters as well as subjective washout visibility and diagnostic confidence benefit from low-kiloelectronvolt virtual monoenergetic images.

Virtual mono-energetic images and iterative image reconstruction: abdominal vessel imaging in the era of spectral detector CT.

AIM: To compare the quality of virtual mono-energetic (VMI) and polychromatic images reconstructed with hybrid iterative (PCIHIR) or model-based reconstruction (PCIMBR) derived from dual-layer spectral detector computed tomography (SDCT) in arterial phase images to visualise the aorta and abdominal main branches. MATERIAL AND METHODS: A retrospective review of 50 patients with abdominal arterial phase scans was undertaken. Attenuation, intraluminal noise, and signal-/contrast-to-noise ratio (S-/CNR) were assessed in the PCIHIR, PCIMBR and VMI40keV, VMI70keV, and VMI100keV images. Contrast, noise, and visualization of soft-plaque, and macro-/micro-calcifications were scored in a blinded reading by two radiologists. RESULTS: VMI40keV yielded highest S-/CNR (p≤0.001). VMI70keV and PCIMBR showed comparable SNR (p≥0.999) and yielded higher SNR than PCIHIR. VMI70keV yielded higher CNR than PCIHIR (p<0.001) and PCIMBR (p<0.045). VMI100keV yielded lowest CNR (p≤0.001) and SNR (p≥0.104). In the subjective analysis, VMI40keV outperformed PCIMBR for contrast and noise, PCIMBR scored better than VMI70keV, and the latter scored better than PCIHIR for these categories (all p<0.001). PCIMBR was superior for depiction of soft-plaque and micro-calcifications (p<0.001). VMI100keV visualized micro-calcifications second best (p<0.001) and matched PCIMBR for the depiction of macro-calcifications (p>0.999), while VMI40keV scored second best for depiction of soft-plaque (p<0.020). CONCLUSIONS: VMI40keV and VMI70keV yield better S-/CNR than PCIHIR and PCIMBR; however, PCIMBR visualized arteriosclerotic plaques best, followed by VMI40keV for depiction of soft-plaque and VMI100keV for macro- and micro-calcification. Based on the present findings, PCIMBR on conventional CT and VMI40keV supplemented by VMI100keV on SDCT are recommended for the diagnostic assessment of abdominal arteries.

Investigation of umbilical venous vessels anatomy and diameters as a guideline for catheter placement in newborns.

Umbilical cord catheters (UCC) are important for the primary care of critically ill newborns. To analyze anatomical variations of the umbilical vein (UV) and its further course, we performed abdominal spiral-CT examinations on stillborns. The aim of the study was to explore the high incidence of mal-positioned UCCs and to improve their positioning. Eighteen stillborns were investigated (29.2 weeks ± 6.7 weeks (IQR)). CTs were performed using either air or contrast medium injection into the UV. We measured the diameter at the narrowest points of (i) the umbilical vein, (ii) the segmental portal vein, (iii) the left portal vein, (iv) the umbilical recess, and (v) the ductus venosus. The branching angles between (a) the umbilical vein and intrahepatic veins and (b) the ductus venosus and umbilical recess were measured. The diameter of the UV increases from 3.4 to 11 mm (median [IQR]:4.6 mm [4.2-6.9]: r2 = 0.64). The left portal vein has a larger diameter (3.6 mm [2.6-4.55]; r2 = 0.43) than the left segmental portal vein (2.3 mm [1.8-2.75]; r2 = 0.23). The diameter of the ductus venosus (2.5 mm [1.6-3.4]; r2 = 0.59) is half that of the umbilical recess (5.1 mm [3.3-6.2]; r2 = 0.43). The most obtuse angle is formed by the junction between the umbilical recess and ductus venosus (151° [133-159]; r2 = 0.001). The branch angle from the outgoing UV into the left portal vein is more obtuse (128° [123-144]; r2 = 0.0001) than that of the segmental portal vein (115° [105-119]; r2 = 0.0001). To avoid mal-positioning, our data suggest the use of a soft catheter. The UV and its extensions are wide enough to admit a 4 Fr. catheter without complete obstruction. Clin. Anat. 31:269-274, 2018. © 2017 Wiley Periodicals, Inc.

[Radiological response assessment of modern immunotherapy using iRECIST]. / Radiologische Responsebeurteilung moderner Immuntherapien mithilfe von iRECIST.

CLINICAL/METHODICAL ISSUE: Modern immunotherapies in oncology show tumor response patterns differing from conventional chemotherapies including initial pseudo-progression. STANDARD RADIOLOGICAL METHODS: Response evaluation criteria in solid tumors (RECIST 1.1) represent the currently most used response criteria for conventional chemotherapy of solid tumors. However, atypical response patterns of immunotherapies are not correctly classified using RECIST 1.1 so that the effectiveness is also incorrectly interpreted. METHODICAL INNOVATIONS: In order to correctly interpret these atypical response patterns, special immune-related response criteria in solid tumors (iRECIST) have been published. In contrast to RECIST 1.1 according to iRECIST an initially unconfirmed progressive disease (iUPD) requires confirmation (iCPD) in clinically stable patients by subsequent control imaging after 4-8 weeks. New lesions are separately assessed within iRECIST. PERFORMANCE: The iRECIST procedure allows a standardized objective assessment of a possible pseudo-progression which can occur in up to 10% of cases depending on the immunomodulating drug and tumor entity. ACHIEVEMENTS: In principle, iRECIST was developed only for usage in trials testing modern immunotherapeutics. PRACTICAL RECOMMENDATIONS: The iRECIST procedure might also be helpful as an additional objective response criterium for clinical treatment decisions, taking the limitations into account.

[Response criteria for malignant melanoma: RECIST and irRC]. / Responsekriterien bei malignem Melanom: RECIST und irRC.

In the field of oncology the response evaluation criteria in solid tumors (RECIST) currently represent the most commonly used and validated radiological response criteria for objective treatment monitoring of conventional chemotherapy. For therapy monitoring of classical cytostatic and cytotoxic tumor therapies RECIST has been tested and successfully validated in many clinical studies. However, with the introduction of novel molecular drugs limitations of these size-based criteria became obvious due to response patterns which are not reflected by RECIST. Thus, for a comprehensive evaluation of modern immunotherapeutic agents new immune-related response criteria (irRC) were developed.This review gives a brief overview of the most important radiological response criteria RECIST 1.0 and 1.1 as well as irRC for malignant melanoma.

[Modern magnetic resonance imaging of the liver]. / Modernes MR-Protokoll für die Leberbildgebung.

Magnetic resonance imaging (MRI) of the liver has become an essential tool in the radiological diagnostics of both focal and diffuse diseases of the liver and is subject to constant change due to technological progress. Recently, important improvements could be achieved by innovations regarding MR hardware, sequences and postprocessing methods. The diagnostic spectrum of MRI could be broadened particularly due to new examination sequences, while at the same time scanning time could be shortened and image quality has been improved. The aim of this article is to explain both the technological background and the clinical application of recent MR sequence developments and to present the scope of a modern MRI protocol for the liver.

Overall survival and central nervous system activity of crizotinib in ROS1-rearranged lung cancer-final results of the EUCROSS trial.

BACKGROUND: In 2019, we reported the first efficacy and safety analysis of EUCROSS, a phase II trial investigating crizotinib in ROS1 fusion-positive lung cancer. At that time, overall survival (OS) was immature and the effect of crizotinib on intracranial disease control remained unclear. Here, we present the final analysis of OS, systemic and intracranial activity, and the impact of co-occurring aberrations. MATERIALS AND METHODS: EUCROSS was a prospective, single-arm, phase II trial. The primary endpoint was best overall response rate (ORR) using RECIST 1.1. Secondary and exploratory endpoints were progression-free survival (PFS), OS, and efficacy in pre-defined subgroups. RESULTS: Median OS of the intention-to-treat population (N = 34) was 54.8 months [95% confidence interval (CI) 20.3 months-not reached (NR); median follow-up 81.4 months] and median all-cause PFS of the response-evaluable population (N = 30) was 19.4 months (95% CI 10.1-32.2 months). Time on treatment was significantly correlated with OS (R = 0.82; P < 0.0001). Patients with co-occurring TP53 aberrations (28%) had a significantly shorter OS [hazard ratio (HR) 11; 95% CI 2.0-56.0; P = 0.006] and all-cause PFS (HR 4.2; 95% CI 1.2-15; P = 0.025). Patients with central nervous system (CNS) involvement at baseline (N = 6; 20%) had a numerically shorter median OS and all-cause PFS. Median intracranial PFS was 32.2 months (95% CI 23.7 months-NR) and the rate of isolated CNS progression was 24%. CONCLUSIONS: Our final analysis proves the efficacy of crizotinib in ROS1-positive lung cancer, but also highlights the devastating impact of TP53 mutations on survival and treatment efficacy. Additionally, our data show that CNS disease control is durable and the risk of CNS progression while on crizotinib treatment is low.

Azole-resistant invasive aspergillosis in a patient with acute myeloid leukaemia in Germany.

We report the first culture-proven case of invasive aspergillosis (IA) caused by azole-resistant Aspergillus fumigatus in a patient with acute myeloid leukaemia in Germany. IA presented as breakthrough infection under posaconazole prophylaxis. Analysis of the resistance mechanism revealed the TR/L98H mutation in the cyp51A gene, which indicates an environmental origin of the strain. This case underscores the need for monitoring azole resistance in Aspergillus spp. and for routine susceptibility testing of moulds.

[Image-guided, minimally invasive surgery and other local therapeutic procedures for primary liver tumors]. / Bildgestützte minimal-invasive Chirurgie und andere lokaltherapeutische Verfahren bei primären Lebertumoren.

BACKGROUND: The incidence of primary liver tumors is rising. Modern minimally invasive, image-guided procedures offer a potentially curative therapy option. OBJECTIVE: The aim of this study was to evaluate the multitude of image-guided minimally invasive procedures concerning their evidence-based effect on local tumor control and overall survival. MATERIAL AND METHODS: A systematic search of MEDLINE focused on hepatocellular cancer, minimally invasive treatment, local ablative therapy, therapeutic stratification and comparative studies was performed. RESULTS: The level of evidence varied greatly depending on the procedure used. The highest quality evidence including prospective randomized studies was found for radiofrequency ablation (RFA) of hepatocellular cancer. The RFA is superior with respect to local tumor control and overall survival in comparison to other ablative procedures. Prospective randomized studies comparing surgery and RFA showed diverging and contradictory results. Microwave ablation and robotic stereotactic irradiation showed sufficient potential in retrospective studies in comparison to RFA and surgery in order to confirm the techniques in randomized studies. There is only anecdotal evidence concerning high intensity focused ultrasound (HIFU) and irreversible electroporation. Percutaneous ethanol injection (PEI), cryoablation and laser-induced thermal therapy (LITT) were inferior techniques to RFA in most studies. CONCLUSION: Minimally invasive resection and local ablative therapies based on structured imaging and image reporting can improve the prognosis of patients with hepatocellular cancer even in patients that exceed the BCLC 0/A stage.

Improved visualization of hypodense liver lesions in virtual monoenergetic images from spectral detector CT: Proof of concept in a 3D-printed phantom and evaluation in 74 patients.

OBJECTIVES: The well-known boost of iodine associated-attenuation in low-keV virtual monoenergetic images (VMI_low) is frequently used to improve visualization of lesions and structures taking up contrast media. This study aimed to evaluate this concept in reverse. Hence to investigate if increased attenuation within the liver allows for improved visualization of little or not-enhancing lesions. METHODS: A 3D-printed phantom mimicking the shape of a human liver exhibiting a lesion in its center was designed and printed. Both, parenchyma- and lesion-mimic were filled with different solutions exhibiting 80/100/120HU and 0/15/40/60HU, respectively. Further, a total of 74 contrast-enhanced studies performed on a spectral detector CT scanner (SDCT) were included in this retrospective study. Patients had MRI or follow-up proven cysts and/or hypodense metastases. VMI of 40-200 keV as well as conventional images (CI) were reconstructed. ROI were placed in lesion and parenchyma(-mimics) on CI and transferred to VMI. Signal- and contrast-to-noise ratio were calculated (S-/CNR). Further, two radiologists independently evaluated image quality. Data was statistically assessed using ANOVA or Wilcoxon-test. RESULTS: In phantoms, S/CNR was significantly higher in VMI_low. The cyst-mimic in highly attenuating parenchyma-mimic on CI yielded a CNR of 6.4 ± 0.8; using VMI_40 keV, mildly hypodense lesion-mimic in poorly attenuating parenchyma-mimic exhibited a similar CNR (5.8 ± 0.9; p ≤ 0.05). The same tendency was observed in patients (cyst in CI/metastasis in VMI_40 keV: 4.4 ± 1.2/3.9 ± 1.8; p ≤ 0.05). Qualitative analysis indicated a benefit of VMI_40 keV (p ≤ 0.05). CONCLUSIONS: VMI_low from SDCT allow for an improved visualization of hypodense focal liver lesions exploiting the concept of contrast blooming in reverse.

Assessment of arterially hyper-enhancing liver lesions using virtual monoenergetic images from spectral detector CT: phantom and patient experience.

PURPOSE: To investigate a benefit from virtual monoenergetic reconstructions (VMIs) for assessment of arterially hyper-enhancing liver lesions in phantom and patients and to compare hybrid-iterative and spectral image reconstructions of conventional images (CI-IR and CI-SR). METHODS: All imaging was performed on a SDCT (Philips Healthcare, Best, The Netherlands). Images of a non-anthropomorphic phantom with a lesion-mimicking insert (containing iodine in water solution) and arterial-phase images from contrast-enhanced patient examinations were evaluated. VMIs (40-200 keV, 10 keV increment), CI-IR, and CI-SR were reconstructed using different strengths of image denoising. ROIs were placed in lesions, liver/matrix, muscle; signal-to-noise, contrast-to-noise, and lesion-to-liver ratios (SNR, CNR, and LLR) were calculated. Qualitatively, 40, 70, and 110 keV and CI images were assessed by two radiologists on five-point Likert scales regarding overall image quality, lesion assessment, and noise. RESULTS: In phantoms, SNR was increased threefold by VMI40keV compared with CI-IR/SR (5.8 ± 1.1 vs. 18.8 ± 2.2, p ≤ 0.001), while no difference was found between CI-IR and CI-SR (p = 1). Denoising was capable of noise reduction by 40%. In total, 20 patients exhibiting 51 liver lesions were assessed. Attenuation was the highest in VMI40keV, while image noise was comparable to CI-IR resulting in a threefold increase of CNR/LLR (CI-IR 1.3 ± 0.8/4.4 ± 2.0, VMI40keV: 3.8 ± 2.7/14.2 ± 7.5, p ≤ 0.001). Subjective lesion delineation was the best in VMI40keV image (p ≤ 0.01), which also provided the lowest perceptible noise and the best overall image quality. CONCLUSIONS: VMIs improve assessment of arterially hyper-enhancing liver lesions since they increase lesion contrast while maintaining low image noise throughout the entire keV spectrum. These data suggest that to consider VMI screening after arterially hyper-enhancing liver lesions.

Does the trabecular bone structure depicted by high-resolution MRI of the calcaneus reflect the true bone structure?

RATIONALE AND OBJECTIVES: The purpose of this study was to compare trabecular bone structure parameters assessed with high-resolution magnetic resonance imaging (HR-MRI) with those determined in specimen sections. METHODS: High-resolution MR images were obtained for 30 calcaneus specimens with a three-dimensional, T1-weighted spin-echo sequence (spatial in-plane resolution 0.195 mm, slice thicknesses of 0.3 and 0.9 mm). Thirty-eight sections were obtained from the specimens, and contact radiography was performed. In the corresponding sections, structural parameters analogous to bone histomorphometry were determined. RESULTS: Significant correlations between MRI-derived structural parameters and those derived from macro pathological sections were found: r values of up to 0.75 were obtained (P < 0.01). The highest correlations were found for apparent bone volume/total volume and trabecular thickness. Image thresholding techniques showed a significant impact on these correlations (P < 0.01). The thinner MR sections were less susceptible to the different thresholding algorithms. CONCLUSIONS: Trabecular bone structure depicted by HR-MR images is significantly correlated with that shown in macro sections (P < 0.01); however, a number of limitations have to be considered, including the substantial impact of thresholding techniques and slice thickness.

MSCT follow-up in malignant lymphoma: comparison of manual linear measurements with semi-automated lymph node analysis for therapy response classification.

PURPOSE: Assignment of semi-automated lymph node analysis compared to manual measurements for therapy response classification of malignant lymphoma in MSCT. MATERIALS AND METHODS: MSCT scans of 63 malignant lymphoma patients before and after 2 cycles of chemotherapy (307 target lymph nodes) were evaluated. The long axis diameter (LAD), short axis diameter (SAD) and bi-dimensional WHO were determined manually and semi-automatically. The time for manual and semi-automatic segmentation was evaluated. The ref. standard response was defined as the mean relative change across all manual and semi-automatic measurements (mean manual/semi-automatic LAD, SAD, semi-automatic volume). Statistical analysis encompassed t-test and McNemar's test for clustered data. RESULTS: Response classification per lymph node revealed semi-automated volumetry and bi-dimensional WHO to be significantly more accurate than manual linear metric measurements. Response classification per patient based on RECIST revealed more patients to be correctly classified by semi-automatic measurements, e. g. 96.0 %/92.9 % (WHO bi-dimensional/volume) compared to 85.7/84.1 % for manual LAD and SAD, respectively (mean reduction in misclassified patients of 9.95 %). Considering the use of correction tools, the time expenditure for lymph node segmentation (29.7 ± 17.4 sec) was the same as with the manual approach (29.1 ± 14.5 sec). CONCLUSION: Semi-automatically derived "lymph node volume" and "bi-dimensional WHO" significantly reduce the number of misclassified patients in the CT follow-up of malignant lymphoma by at least 10 %. However, lymph node volumetry does not outperform bi-dimensional WHO.

Current role and future perspective of MRI for diagnosis and characterization of renal cell carcinoma.

During the past years, magnetic resonance imaging (MRI) has been established as a reliable method for examination of the kidneys. Modern MRI systems enable to visualize renal masses with a high spatial resolution. This enables not only to differentiate between benign lesions and renal cancer but also to define the tumor stage with high accuracy. The impact of a precise preoperative staging has increased significantly due to stage adapted therapy approaches such as nephron sparing surgery or local ablative techniques (e.g. radiofrequency ablation). Tumor-related infiltration of the renal pelvis, infiltration of the perinephric fat or a tumor thrombus within the inferior caval vein has to be diagnosed with high accuracy to enable these stage adapted treatment regimens. This article introduces into clinically established "morphologic" MRI techniques for diagnosis and staging of renal cell carcinoma (RCC). Besides detection and staging of kidney cancer, the recent development of molecularly targeted therapies in patients with metastatic or non-operable tumors has led to novel diagnostic demands. To evaluate treatment efficiency, more information than just tumor morphology should be provided. Functional imaging techniques including dynamic contrast enhanced (DCE) MRI, diffusion weighted imaging (DWI), arterial spin labeling (ASL) and MR-spectroscopy are being investigated in preclinical and clinical trials. While some new techniques have shown promising results for a broad clinical application, others seem to be suited for dedicated questions only.

[Modern magnetic resonance procedures for assessing tumor response]. / Moderne MR-Verfahren zur Beurteilung der Tumorresponse.

Magnetic resonance imaging (MRI) is a mainstay in oncological imaging with respect to tumor detection, characterization and treatment monitoring. Besides quantifying metric changes of tumor tissue, a wide range of different other surrogate parameters of therapy response can be imaged and quantified by MRI. Early monitoring of treatment success is critical both for medical and economical reasons specifically with more expensive target-specific drugs entering the clinical arena. Dynamic contrast-enhanced (DCE) and steady state MRI can help to assess tumor perfusion and vessel permeability. The cellular state of tissue can be measured by diffusion-weighted imaging (DWI) and metabolic changes can be monitored by MR spectroscopy (MRS). New target-specific contrast agents potentially allow selective imaging of apoptotic events.This review aims to give a brief overview of new MR-based imaging approaches to assess tumor response to new target-specific therapy regimes, with special emphasis on anti-angiogenic and antivascular treatment effects.

MR and optical approaches to molecular imaging.

With an increasing understanding of the molecular basis of disease, various new imaging targets have recently been defined that potentially allow for an early, sensitive, and specific diagnosis of disease or monitoring of treatment response. Different approaches to depict these molecular structures in vivo are currently being explored by the molecular imaging community. We briefly review methodologies for molecular imaging by magnetic resonance imaging and optical methods. Special emphasis is put on different contrast agent designs (e.g., targeted and smart probes). New technical developments in optical imaging are briefly discussed. In addition, current research results are put into a clinical perspective to elucidate the potential merits one might expect from this new research field.