Relaxation induced by ferritin: a better understanding for an improved MRI iron quantification

Gossuin, Yves; Müller, Robert N.; Gillis, Pierre

doi:10.1002/nbm.903

Cited by 113 publications

(107 citation statements)

References 47 publications

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“…A third limitation stems from our analysis of ferritin, which relies on in vitro T 2 relaxivity values of purified protein. There are likely to be significant differences between in vitro and in vivo holoferritin relaxivity values (23). In addition, r 2 values in vivo may be tissue-type dependent, and thus high-accuracy contrast modeling may be needed to account for these differences.…”

Section: Discussionmentioning

confidence: 99%

Theoretical MRI contrast model for exogenous T₂ agents

Mills

Ahrens

2007

Magnetic Resonance in Med

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The rational development of new generations of MRI contrast agents (CAs) requires a scheme for predicting contrast enhancement. Previous contrast predictions have been based largely on empirical results in specific systems. Here we present a general theoretical model for evaluating the minimum concentration of T 2 CA required for satisfactory image contrast. This analytic contrast model is applicable to a wide range of T 2 -type agents and delivery scenarios, and requires only a few readily evaluated parameters. We demonstrated the model by predicting contrast produced by superparamagnetic ferumoxide and the iron storage protein, ferritin. We then experimentally verified the predictions using suspensions of Feridexா and ferritin in phantoms. The model was also used to compare the contrast efficacy of the metal ions in two clinically approved T 1 -and T 2 -type CAs. In the Appendix we present a numerical formalism that is useful for relating image contrast and agent concentration when gradient-echo (GRE) T* 2 -weighted (T There is great interest in developing new generations of MRI contrast agents (CAs) that can be used for diagnostic purposes, therapeutic monitoring, and to further our understanding of diseases. New generations of agents can often provide MRI contrast for specific cell types, detect the presence of specific molecules, such as enzymes and nucleic acids (1-3), and be responsive to physiology.Superparamagnetic iron oxide (SPIO) CAs are widely used as a platform for many of these emerging cellularmolecular applications (1). SPIO agents typically consist of an iron-oxide nanocrystal that is coated with dextran or polymer and have a net median diameter of 10 -100 nm. SPIO particles perturb the static magnetic field out to a distance on the order of ϳ50 2 times its diameter, resulting in a dramatic reduction in T 2 of nearby water molecules. The resulting images exhibit hypointense regions, indicating agent accumulation. Unmodified SPIO particles, such as Resovist, Feridex, and Combidex, have been used for cellular imaging (4) and are FDA-approved for detecting liver lesions and distinguishing between normal and cancerous lymph nodes. SPIO particles with surfaces conjugated to targeting entities, such as peptides or antibodies, have also been described (4). Intracellular applications of SPIO for cell-tracking in animal models is a rapidly evolving research area (5), and the clinical translation of these techniques is already in the early stage (6).In addition, T 2 -type CAs are included in a new category of intracellular labeling approaches that utilize genetically-encoded metalloproteins (2,7). In this approach, metalloproteins from the ferritin family are expressed in specific host tissues. These iron-storage metalloproteins effectively become a superparamagnetic CA by sequestering endogenous iron from the organism and thus imparting MRI contrast to targeted tissues.For useful images to be generated, CAs must accumulate in cells or tissues in adequate concentrations. Moreover, too high of a concentra...

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Section: Discussionmentioning

confidence: 99%

Theoretical MRI contrast model for exogenous T₂ agents

Mills

Ahrens

2007

Magnetic Resonance in Med

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“…1 A 57-year-old man with liver cirrhosis. A hyperintense lesion is present in the globus pallidus (white arrow) on sagittal T1WI due to manganese deposition and a low signal intensity on T2WI [55][56][57][58]. As the correlation between the iron content and T2WI is questionable, T2*-weighted imaging [59], susceptibility-weighted imaging [60], and quantitative susceptibility mapping [61,62] have been tested as methods of estimating the iron content.…”

Section: Ironmentioning

confidence: 99%

Contribution of metals to brain MR signal intensity: review articles

et al. 2016

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“…Ferritins are ubiquitous iron storage proteins and recent studies have shown that human ferritin can be used as a reporter of gene expression for MRI. 103 Bacteria also encode three classes of ferritintype molecules which Hill et al 104 have recently investigated for their potential as MRI reporter genes. 104 Tumor specific induction of bacterioferritin-expression in colonised murine tumors resulted in contrast changes within the tumors.…”

Section: Magnetic Resonance Imagingmentioning

confidence: 99%

Bacterial vectors for imaging and cancer gene therapy: a review

et al. 2012

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The significant burden of resistance to conventional anticancer treatments in patients with advanced disease has prompted the need to explore alternative therapeutic strategies. The challenge for oncology researchers is to identify a therapy which is selective for tumors with limited toxicity to normal tissue. Engineered bacteria have the unique potential to overcome traditional therapies' limitations by specifically targeting tumors. It has been shown that bacteria are naturally capable of homing to tumors when systemically administered resulting in high levels of replication locally, either external to (non-invasive species) or within tumor cells (pathogens). Pre-clinical and clinical investigations involving bacterial vectors require relevant means of monitoring vector trafficking and levels over time, and development of bacterial-specific real-time imaging modalities are key for successful development of clinical bacterial gene delivery. This review discusses the currently available imaging technologies and the progress to date exploiting these for monitoring of bacterial gene delivery in vivo.Cancer Gene Therapy ( INTRODUCTIONAlthough the potential anti-cancer effects of acquired bacterial infection have been evident for over 120 years and the presence of bacteria in excised tumors has been noted for over 60 years, 1 it is only in more recent times that the tumor-specific growth of bacteria has been considered for therapeutic purposes. While the precise mechanism(s) behind preferential bacterial tumor colonization remain poorly understood, this phenomenon must relate to unique tumor attributes that separate them from healthy tissues. Factors such as the irregular blood supply; local immune suppression; inflammation; and unique nutrient supply (e.g., purines) in tumors have been proposed to play a role. 2 Bacterial entry into the tumor environment is proposed to be facilitated by the leaky vasculature. Cancer cells are characterized by an aberrantly accelerated metabolism and proliferation leading to an imbalance of oxygen supply and consumption which is a major causative factor of tumor hypoxia. 3 The hypoxic nature of solid tumors enhances the growth of anaerobic and facultatively anaerobic bacteria. In addition, these areas with low oxygen and high interstitial pressure are considered to be an immunological sanctuary, where bacterial clearance mechanisms are greatly inhibited. 4 Necrotic regions are also rich in nutrients favoured by bacteria due to tumor cell turnover. However, tumor selective bacterial colonization now appears to be both bacterial species and tumor origin independent, since aerobic bacteria are also capable of colonising tumors, and even small tumors lacking an anaerobic center are colonised. See Figure 1 for proposed mechanisms.Invasive bacteria can internalize and replicate within tumor cells, while non-invasive bacteria grow externally to tumor cells, within the tumor micro-environment. 5 The tumor selective growth of bacteria has made them an attractive vehicle for the delivery of ...

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Relaxation induced by ferritin: a better understanding for an improved MRI iron quantification

Cited by 113 publications

References 47 publications

Theoretical MRI contrast model for exogenous T₂ agents

Theoretical MRI contrast model for exogenous T₂ agents

Contribution of metals to brain MR signal intensity: review articles

Bacterial vectors for imaging and cancer gene therapy: a review

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Relaxation induced by ferritin: a better understanding for an improved MRI iron quantification

Cited by 113 publications

References 47 publications

Theoretical MRI contrast model for exogenous T2 agents

Theoretical MRI contrast model for exogenous T2 agents

Contribution of metals to brain MR signal intensity: review articles

Bacterial vectors for imaging and cancer gene therapy: a review

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Theoretical MRI contrast model for exogenous T₂ agents

Theoretical MRI contrast model for exogenous T₂ agents