Cone-beam CT-based Navigation With Augmented Fluoroscopy of the Airways for Image-guided Bronchoscopic Biopsy of Peripheral Pulmonary Nodules: A Prospective Clinical Study.

BACKGROUND: Cone-beam computed tomography (CBCT) and augmented fluoroscopy (AF), in which intraprocedural CBCT data is fused with fluoroscopy, have been utilized as a novel image-guidance technique for biopsy of peripheral pulmonary lesions. The aim of this clinical study is to determine the safety and diagnostic performance of CBCT-guided bronchoscopy with advanced software tools for procedural planning and navigational guidance with AF of the airways for biopsy of peripheral pulmonary nodules. METHODS: Fifty-two consecutive subjects were prospectively enrolled in the AIRWAZE study (December 2018 to October 2019). Image-guided bronchoscopic biopsy procedures were performed under general anesthesia with specific ventilation protocols in a hybrid operating room equipped with a ceiling-mounted C-arm system. Procedural planning and image-guided bronchoscopy with CBCT and AF were performed using the Airwaze investigational device. RESULTS: A total of 58 pulmonary lesions with a median size of 19.0 mm (range 7 to 48 mm) were biopsied. The overall diagnostic yield at index procedure was 87.9% (95% CI: 77.1%-94.0%). No severe adverse events related to CBCT-guided bronchoscopy, such as pneumothorax, bleeding, or respiratory failure, were observed. CONCLUSION: CBCT-guided bronchoscopic biopsy with augmented fluoroscopic views of the airways and target lesion for navigational guidance is technically feasible and safe. Three-dimensional image-guided navigation biopsy is associated with high navigational success and a high diagnostic yield for peripheral pulmonary nodules.

Cone-beam CT and Augmented Fluoroscopy-guided Navigation Bronchoscopy: Radiation Exposure and Diagnostic Accuracy Learning Curves.

BACKGROUND: The endobronchial diagnosis of peripheral lung lesions suspected of lung cancer remains a challenge from a navigation as well as an adequate tissue sampling perspective. Cone-beam computed tomography (CBCT) guidance is a relatively new technology and allows for 3-dimensional imaging confirmation as well as navigation and biopsy guidance, but, also involves radiation. This study investigates how radiation exposure and diagnostic accuracy in the CBCT-guided navigation bronchoscopy evolves with increasing experience, and, with a specific tailoring of CBCT and fluoroscopic imaging protocols towards the procedure. PATIENTS AND METHODS: In this observational clinical trial, all 238 consecutive patients undergoing a CBCT-guided navigation bronchoscopy from the start of our CBCT-guided navigation bronchoscopy program (December 2017) until June 2020 were included. Procedural dose characteristics and diagnostic accuracy are reported as a function of time. RESULTS: Procedural radiation exposure as measured by the dose area product initially was 47.5 Gy·cm2 (effective dose: 14.3 mSv) and gradually reduced to 25.4 Gy·cm2 (5.8 mSv). The reduction in fluoroscopic dose area product was highest, from 19.0 Gy·cm2 (5.2 mSv) to 2.2 Gy·cm2 (0.37 mSv, 88% reduction), despite a significant increase of fluoroscopy time. The diagnostic accuracy of navigation bronchoscopy increased from 72% to 90%. CONCLUSION: A significant learning effect can be seen in the radiation safety and diagnostic accuracy of a CBCT-guided and augmented fluoroscopy-guided navigation bronchoscopy. With increasing experience and tailoring of imaging protocols to the procedure, the procedural accuracy improved, while the effective dose for patients and staff was reduced.

Looking through the eyes of the multidisciplinary team: the design and clinical evaluation of a decision support system for lung cancer care.

BACKGROUND: Decision-making in lung cancer is complex due to a rapidly increasing amount of diagnostic data and treatment options. The need for timely and accurate diagnosis and delivery of care demands high-quality multidisciplinary team (MDT) collaboration and coordination. Clinical decision support systems (CDSSs) can potentially support MDTs in constructing a shared mental model of a patient case. This enables the team to assess the strength and completeness of collected diagnostic data, stratification for the right personalized therapy driven by clinical stage and other treatment-influencing factors, and adapt care management strategies when needed. Current CDSSs often have a suboptimal fit into the decision-making workflow, which hampers their impact in clinical practice. METHODS: A CDSS for multidisciplinary decision-making in lung cancer was designed to support the abovementioned goals through presentation of relevant clinical data in line with existing mental model structures of the MDT members. The CDSS was tested in a simulated multidisciplinary tumor board meeting for primary diagnosis and treatment selection, based on de-identified primary lung cancer cases (n=8). Decision course analysis, eye-tracking data and questionnaires were used to assess the impact of the CDSS on constructing shared mental models to improve the decision-making process and outcome. RESULTS: The CDSS supported the team in their self-correcting capacity for accurate diagnosis and TNM classification. It enabled cross-validation of diagnostic findings, surfaced discordance between diagnostic tests and facilitated cancer staging according the diagnostic evidence, as well as spotting contra-indications for personalized treatment selection. CONCLUSIONS: This study shows the potential of CDSS on clinical decision making, when these systems are properly designed in line with clinical thinking. The presented setup enables assessment of the impact of CDSS design on clinical decision making and optimization of CDSSs to maximize their effect on decision quality and confidence.

Thermal combination therapies for local drug delivery by magnetic resonance-guided high-intensity focused ultrasound.

Several thermal-therapy strategies such as thermal ablation, hyperthermia-triggered drug delivery from temperature-sensitive liposomes (TSLs), and combinations of the above were investigated in a rhabdomyosarcoma rat tumor model (n = 113). Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) was used as a noninvasive heating device with precise temperature control for image-guided drug delivery. For the latter, TSLs were prepared, coencapsulating doxorubicin (dox) and [Gd(HPDO3A)(H2O)], and injected in tumor-bearing rats before MR-HIFU treatment. Four treatment groups were defined: hyperthermia, ablation, hyperthermia followed by ablation, or no HIFU. The intratumoral TSL and dox distribution were analyzed by single-photon emission computed tomography (SPECT)/computed tomography (CT), autoradiography, and fluorescence microscopy. Dox biodistribution was quantified and compared with that of nonliposomal dox. Finally, the treatment efficacy of all heating strategies plus additional control groups (saline, free dox, and Caelyx) was assessed by tumor growth measurements. All HIFU heating strategies combined with TSLs resulted in cellular uptake of dox deep into the interstitial space and a significant increase of tumor drug concentrations compared with a treatment with free dox. Ablation after TSL injection showed [Gd(HPDO3A)(H2O)] and dox release along the tumor rim, mirroring the TSL distribution pattern. Hyperthermia either as standalone treatment or before ablation ensured homogeneous TSL, [Gd(HPDO3A)(H2O)], and dox delivery across the tumor. The combination of hyperthermia-triggered drug delivery followed by ablation showed the best therapeutic outcome compared with all other treatment groups due to direct induction of thermal necrosis in the tumor core and efficient drug delivery to the tumor rim.

Bioresponsive probes for molecular imaging: concepts and in vivo applications.

Molecular imaging is a powerful tool to visualize and characterize biological processes at the cellular and molecular level in vivo. In most molecular imaging approaches, probes are used to bind to disease-specific biomarkers highlighting disease target sites. In recent years, a new subset of molecular imaging probes, known as bioresponsive molecular probes, has been developed. These probes generally benefit from signal enhancement at the site of interaction with its target. There are mainly two classes of bioresponsive imaging probes. The first class consists of probes that show direct activation of the imaging label (from "off" to "on" state) and have been applied in optical imaging and magnetic resonance imaging (MRI). The other class consists of probes that show specific retention of the imaging label at the site of target interaction and these probes have found application in all different imaging modalities, including photoacoustic imaging and nuclear imaging. In this review, we present a comprehensive overview of bioresponsive imaging probes in order to discuss the various molecular imaging strategies. The focus of the present article is the rationale behind the design of bioresponsive molecular imaging probes and their potential in vivo application for the detection of endogenous molecular targets in pathologies such as cancer and cardiovascular disease.

Temperature-sensitive paramagnetic liposomes for image-guided drug delivery: Mn(2+) versus [Gd(HPDO3A)(H2O)].

Temperature-sensitive liposomes (TSLs) loaded with doxorubicin (Dox), and Magnetic Resonance Imaging contrast agents (CAs), either manganese (Mn(2+)) or [Gd(HPDO3A)(H2O)], provide the advantage of drug delivery under MR image guidance. Encapsulated MRI CAs have low longitudinal relaxivity (r1) due to limited transmembrane water exchange. Upon triggered release at hyperthermic temperature, the r1 will increase and hence, provides a means to monitor drug distribution in situ. Here, the effects of encapsulated CAs on the phospholipid bilayer and the resulting change in r1 were investigated using MR titration studies and (1)H Nuclear Magnetic Relaxation Dispersion (NMRD) profiles. Our results show that Mn(2+) interacted with the phospholipid bilayer of TSLs and consequently, reduced doxorubicin retention capability at 37°C within the interior of the liposomes over time. Despite that, Mn(2+)-phospholipid interaction resulted in higher r1 increase, from 5.1±1.3mM(-1)s(-1) before heating to 32.2±3mM(-1)s(-1) after heating at 60MHz and 37°C as compared to TSL(Gd,Dox) where the longitudinal relaxivities before and after heating were 1.2±0.3mM(-1)s(-1) and 4.4±0.3mM(-1)s(-1), respectively. Upon heating, Dox was released from TSL(Mn,Dox) and complexation of Mn(2+) to Dox resulted in a similar Mn(2+) release profile. From 25 to 38°C, r1 of [Gd(HPDO3A)(H2O)] gradually increased due to increase transmembrane water exchange, while no Dox release was observed. From 38°C, the release of [Gd(HPDO3A)(H2O)] and Dox was irreversible and the release profiles coincided. By understanding the non-covalent interactions between the MRI CAs and phospholipid bilayer, the properties of the paramagnetic TSLs can be tailored for MR guided drug delivery.

Relaxometric studies of gadolinium-functionalized perfluorocarbon nanoparticles for MR imaging.

Fluorine MRI ((19) F MRI) is receiving an increasing attention as a viable alternative to proton-based MRI ((1) H MRI) for dedicated application in molecular imaging. The (19) F nucleus has a high gyromagnetic ratio, a 100% natural abundance and is furthermore hardly present in human tissues allowing for hot spot MR imaging. The applicability of (19) F MRI as a molecular and cellular imaging technique has been exploited, ranging from cell tracking to detection and imaging of tumors in preclinical studies. In addition to applications, developing new contrast materials with improved relaxation properties has also been a core research topic in the field, since the inherently low longitudinal relaxation rates of perfluorocarbon compounds result in relatively low imaging efficiency. Borrowed from (1) H MRI, the incorporation of lanthanides, specifically Gd(III) complexes, as signal modulating ingredients in the nanoparticle formulation has emerged as a promising approach to improvement of the fluorine signal. Three different perfluorocarbon emulsions were investigated at five different magnetic field strengths. Perfluoro-15-crown-5-ether was used as the core material and Gd(III)DOTA-DSPE, Gd(III)DOTA-C6-DSPE and Gd(III)DTPA-BSA as the relaxation altering components. While Gd(III)DOTA-DSPE and Gd(III)DOTA-C6-DSPE were favorable constructs for (1) H NMR, Gd(III)DTPA-BSA showed the strongest increase in (19F) R(1). These results show the potential of the use of paramagnetic lipids to increase (19F) R(1) at clinical field strengths (1.5-3 T). At higher field strengths (6.3-14 T), gadolinium does not lead to an increase in (19F) R(1) compared with emulsions without gadolinium, but leads to an significant increase in (19F) R(2). Our data therefore suggest that the most favorable situation for fluorine measurements is at high magnetic fields without the inclusion of gadolinium constructs.

Magnetic resonance guided high-intensity focused ultrasound for image-guided temperature-induced drug delivery.

Magnetic resonance guided high-intensity focused ultrasound (MR-HIFU) is a versatile technology platform for noninvasive thermal therapies in oncology. Since MR-HIFU allows heating of deep-seated tissue to well-defined temperatures under MR image guidance, this novel technology has great potential for local heat-mediated drug delivery from temperature-sensitive liposomes (TSLs). In particular, MR provides the ability for image guidance of the drug delivery when an MRI contrast agent is co-encapsulated with the drug in the aqueous lumen of the liposomes. Monitoring of the tumor drug coverage offers possibilities for a personalized thermal treatment in oncology. This review focuses on MR-HIFU as a noninvasive technology platform, temperature-sensitive liposomal formulations for drug delivery and image-guided drug delivery, and the effect of HIFU-induced hyperthermia on the TSL and drug distribution. Finally, the opportunities and challenges of localized MR-HIFU-mediated drug delivery from temperature-sensitive liposomes in oncology are discussed.

Multifunctional liposomes for MRI and image-guided drug delivery.

Liposomes are a class of nanovesicles that have been explored extensively in the biomedical arena for early diagnosis and treatment of disease. In recent years, several liposomal drug formulations have been clinically approved in oncology. In a modular approach, the properties of liposomes can be tailored for combined molecular MRI, therapy and image-guided delivery of therapeutic drugs. Over the last year, extensive research has been performed in the authors laboratory on paramagnetic liposomes as innovative imaging probes for the detection of specific molecular or cellular targets and image-guided drug delivery using multifunctional, temperature-sensitive liposomes. A number of key achievements by the authors group will be highlighted in this research spotlight.

Lanthanide-loaded erythrocytes as highly sensitive chemical exchange saturation transfer MRI contrast agents.

Chemical exchange saturation transfer (CEST) agents are a new class of frequency-encoding MRI contrast agents with a great potential for molecular and cellular imaging. As for other established MRI contrast agents, the main drawback deals with their low sensitivity. The sensitivity issue may be tackled by increasing the number of exchanging protons involved in the transfer of saturated magnetization to the "bulk" water signal. Herein we show that the water molecules in the cytoplasm of red blood cells can be exploited as source of exchangeable protons provided that their chemical shift is properly shifted by the intracellular entrapment of a paramagnetic shift reagent. The sensitivity of this system is the highest displayed so far among CEST agents (less than 1 pM of cells), and the natural origin of this system makes it suitable for in vivo applications. The proposed Ln-loaded RBCs may be proposed as reporters of the blood volume in the tumor region.

Paramagnetic liposomes for molecular MRI and MRI-guided drug delivery.

Liposomes are a versatile class of nanoparticles with tunable properties, and multiple liposomal drug formulations have been clinically approved for cancer treatment. In recent years, an extensive library of gadolinium (Gd)-containing liposomal MRI contrast agents has been developed for molecular and cellular imaging of disease-specific markers and for image-guided drug delivery. This review discusses the advances in the development and novel applications of paramagnetic liposomes in molecular and cellular imaging, and in image-guided drug delivery. A high targeting specificity has been achieved in vitro using ligand-conjugated paramagnetic liposomes. On targeting of internalizing cell receptors, the effective longitudinal relaxivity r1 of paramagnetic liposomes is modulated by compartmentalization effects. This provides unique opportunities to monitor the biological fate of liposomes. In vivo contrast-enhanced MRI studies with nontargeted liposomes have shown the extravasation of liposomes in diseases associated with endothelial dysfunction, such as tumors and myocardial infarction. The in vivo use of targeted paramagnetic liposomes has facilitated the specific imaging of pathophysiological processes, such as angiogenesis and inflammation. Paramagnetic liposomes loaded with drugs have been utilized for therapeutic interventions. MR image-guided drug delivery using such liposomes allows the visualization and quantification of local drug delivery.

SPECT/CT imaging of temperature-sensitive liposomes for MR-image guided drug delivery with high intensity focused ultrasound.

The goal of this study was to investigate the blood kinetics and biodistribution of temperature-sensitive liposomes (TSLs) for MR image-guided drug delivery. The co-encapsulated doxorubicin and [Gd(HPDO3A)(H2O)] as well as the ¹¹¹In-labeled liposomal carrier were quantified in blood and organs of tumor bearing rats. After TSL injection, mild hyperthermia (T=42 °C) was induced in the tumor using high intensity focused ultrasound under MR image-guidance (MR-HIFU). The biodistribution of the radiolabeled TSLs was investigated using SPECT/CT imaging, where the highest uptake of ¹¹¹In-labeled TSLs was observed in the spleen and liver. The MR-HIFU-treated tumors showed 4.4 times higher liposome uptake after 48 h in comparison with controls, while the doxorubicin concentration was increased by a factor of 7.9. These effects of HIFU-treatment are promising for applications in liposomal drug delivery to tumors.

Magnetic resonance guided high-intensity focused ultrasound mediated hyperthermia improves the intratumoral distribution of temperature-sensitive liposomal doxorubicin.

OBJECTIVES: The aim of this study was to investigate the intratumoral distribution of a temperature-sensitive liposomal carrier and its encapsulated compounds, doxorubicin, and a magnetic resonance (MR) imaging contrast agent after high-intensity focused ultrasound (HIFU)-mediated hyperthermia-induced local drug release. MATERIALS AND METHODS: (111)In-labeled temperature-sensitive liposomes encapsulating doxorubicin and [Gd(HPDO3A) (H(2)O)] were injected intravenously in the tail vein of rats (n = 12) bearing a subcutaneous rhabdomyosarcoma tumor on the hind leg. Immediately after the injection, local tumor hyperthermia (2 × 15 minutes) was applied using a clinical 3 T MR-HIFU system. Release of [Gd(HPDO3A)(H(2)O)] was studied in vivo by measuring the longitudinal relaxation rate R(1) with MR imaging. The presence of the liposomal carriers and the intratumoral distribution of doxorubicin were imaged ex vivo with autoradiography and fluorescence microscopy, respectively, for 2 different time points after injection (90 minutes and 48 hours). RESULTS: In hyperthermia-treated tumors, radiolabeled liposomes were distributed more homogeneously across the tumor than in the control tumors (coefficient of variation(hyp, 90 min) = 0.7 ± 0.2; coefficient of variation(cntrl, 90 min) = 1.1 ± 0.2). At 48 hours after injection, the liposomal accumulation in the tumor was enhanced in the hyperthermia group in comparison with the controls. A change in R(1) was observed in the HIFU-treated tumors, suggesting release of the contrast agent. Fluorescence images showed perivascular doxorubicin in control tumors, whereas in the HIFU-treated tumors, the delivered drug was spread over a much larger area and also taken up by tumor cells at a larger distance from blood vessels. CONCLUSIONS: Treatment with HIFU hyperthermia not only improved the immediate drug delivery, bioavailability, and intratumoral distribution but also enhanced liposomal accumulation over time. The sum of these effects may have a significant contribution to the therapeutic outcome.

Hyperthermia-triggered drug delivery from temperature-sensitive liposomes using MRI-guided high intensity focused ultrasound.

In the continuous search for cancer therapies with a higher therapeutic window, localized temperature-induced drug delivery may offer a minimal invasive treatment option. Here, a chemotherapeutic drug is encapsulated into a temperature-sensitive liposome (TSL) that is released at elevated temperatures, for example, when passing through a locally heated tumor. Consequently, high drug levels in the tumor tissue can be achieved, while reducing drug exposure to healthy tissue. Although the concept of temperature-triggered drug delivery was suggested more than thirty years ago, several chemical and technological challenges had to be addressed to advance this approach towards clinical translation. In particular, non-invasive focal heating of tissue in a controlled fashion remained a challenge. For the latter, high intensity focused ultrasound (HIFU) allows non-invasive heating to establish hyperthermia (40-45 °C) of tumor tissue over time. Magnetic resonance imaging (MRI) plays a pivotal role in this procedure thanks to its superb spatial resolution for soft tissue as well as the possibility to acquire 3D temperature information. Consequently, MRI systems emerged with an HIFU ultrasound transducer embedded in the patient bed (MR-HIFU), where the MRI is utilized for treatment planning, and to provide spatial and temperature feedback to the HIFU. For tumor treatment, the lesion is heated to 42 °C using HIFU. At this temperature, the drug-loaded TSLs release their payload in a quantitative fashion. The concept of temperature-triggered drug delivery has been extended to MR image-guided drug delivery by the co-encapsulation of a paramagnetic MRI contrast agent in the lumen of TSLs. This review will give an overview of recent developments in temperature-induced drug delivery using HIFU under MRI guidance.

In vivo temperature controlled ultrasound-mediated intracellular delivery of cell-impermeable compounds.

Many chemotherapeutic drugs are characterized by high systemic toxicity and/or suffer from limited bioavailability. Thermosensitive liposomes (TSLs) encapsulating drugs in their aqueous lumen are promising activatable nanocarriers for ultrasound (US)-mediated drug delivery in response to mild hyperthermia. On the other hand, US is known to locally break biological barriers and as a consequence enable internalization of molecules. In this work, a two-step protocol for intracellular delivery of cell-impermeable molecules comprising of US-induced permeabilization followed by temperature-controlled release of the model drug from thermosensitive liposomes has been developed. TSLs containing TO-PRO-3, a cell-impermeable molecule that displays a significant increase in fluorescence upon binding to nucleic acids thus serving as a 'sensor' for internalization have been prepared and characterized in detail. US-mediated permeabilization followed by temperature-controlled release was applied to tumor bearing mice following i.v. injection of TSLs and microbubbles. The efficacy of this approach was evaluated by in vivo fluorescence imaging followed by histological analysis. A 2.4-fold increase of fluorescence signal was observed and intracellular delivery of TO-PRO-3 was confirmed by a characteristic nuclear staining. These results demonstrate the feasibility of novel drug delivery system to tumors comprising of local cell permeabilization by US followed by in situ release of the payload from thermosensitive liposomes. Possible applications include local and controlled intracellular delivery of molecules with otherwise limited bioavailability.

Iopamidol as a responsive MRI-chemical exchange saturation transfer contrast agent for pH mapping of kidneys: In vivo studies in mice at 7 T.

Iopamidol (Isovue®-Bracco Diagnostic Inc.) is a clinically approved X-Ray contrast agent used in the last 30 years for a wide variety of diagnostic applications with a very good clinical acceptance. Iopamidol contains two types of amide functionalities that can be exploited for the generation of chemical exchange saturation transfer effect. The exchange rate of the two amide proton pools is markedly pH-dependent. Thus, a ratiometric method for pH assessment has been set-up based on the comparison of the saturation transfer effects induced by selective irradiation of the two resonances. This ratiometric approach allows to rule out the concentration effect of the contrast agent and provides accurate pH measurements in the 5.5-7.4 range. Upon injection of Iopamidol into healthy mice, it has been possible to acquire pH maps of kidney regions. Furthermore, it has been also shown that the proposed method is able to report about pH-changes induced in control mice fed with acidified or basified water for a period of a week before image acquisition.

Magnetic resonance imaging of high intensity focused ultrasound mediated drug delivery from temperature-sensitive liposomes: an in vivo proof-of-concept study.

Temperature-sensitive liposomes (TSLs) co-encapsulating doxorubicin and 250 mM [Gd(HPDO3A)(H2O)] were evaluated for HIFU-mediated drug delivery under MR image guidance. In vitro studies showed simultaneous and quantitative release of the drug and the MRI contrast agent from the lumen of the TSLs at 42°C, while no leakage was observed over 1 h at 37°C. In a proof-of-concept study, local hyperthermia has been applied for 30 min in 9L rat tumors using a clinical MR-HIFU system. The local temperature-triggered release of [Gd(HPDO3A)(H2O)] was monitored with interleaved T1 mapping of the tumor tissue. A good correlation between the ΔR1, the uptake of doxorubicin and the gadolinium concentration in the tumor was found, implying that the in vivo release of doxorubicin from TSLs can be probed in situ with the longitudinal relaxation time of the co-released MRI contrast agent.

Temperature-sensitive liposomes for doxorubicin delivery under MRI guidance.

Local drug delivery of doxorubicin holds promise to improve the therapeutic efficacy and to reduce toxicity profiles. Here, we investigated the release of doxorubicin and [Gd(HPDO3A)(H(2)O)] from different temperature-sensitive liposomes for applications in temperature-induced drug delivery under magnetic resonance image guidance. In particular, two temperature-sensitive systems composed of DPPC:MPPC:DPPE-PEG2000 (low temperature-sensitive liposomes, LTSL) and DPPC:HSPC:cholesterol:DPPE-PEG2000 (traditional temperature-sensitive liposomes, TTSL) were investigated. The co-encapsulation of [Gd(HPDO3A)(H(2)O)], a clinically approved MRI contrast agent, did not influence the encapsulation and release of doxorubicin. The LTSL system showed a higher leakage of doxorubicin at 37 degrees C, but a faster release of doxorubicin at 42 degrees C compared to the TTSL system. Furthermore, the rapid release of both doxorubicin and the MRI contrast agent from the liposomes occurred near the melting phase transition temperature, making it possible to image the release of doxorubicin using MRI.

A temperature-sensitive liposomal 1H CEST and 19F contrast agent for MR image-guided drug delivery.

A novel temperature-sensitive liposomal MRI contrast agent has been developed, which allows drug carrier localization using (1)H CEST with simultaneous quantification of the drug release using (19)F MR imaging in response to a local temperature increase.