Risk factors for relapse of immune-related pneumonitis after 6-week oral prednisolone therapy: a follow-up analysis of a phase II study.

BACKGROUND: Immune-related pneumonitis (irP) is one of the most important immune-related adverse events caused by immune checkpoint inhibitors (ICIs). After corticosteroid therapy irP frequently relapses, which can interfere with cancer therapy. However, risk factors for irP relapse are unknown. METHODS: This study was a follow-up analysis of a phase II study that evaluated 56 patients with grade ≥ 2 irP treated with oral prednisolone, 1 mg/kg/day, tapered over 6 weeks. Clinical factors including patient characteristics, blood test findings, and response to prednisolone therapy were assessed to identify risk factors for irP relapse using the Fine-Gray test. RESULTS: Among 56 patients with irP, 22 (39.3%) experienced irP relapse after 6 weeks of prednisolone therapy during the follow-up observation period. Radiographic organising pneumonia (OP) pattern and duration to irP onset ≥ 100 days from ICI initiation were determined to be significant risk factors for irP relapse in a multivariate Fine-Gray test (hazard ratio [HR] = 3.17, 95% CI 1.37-7.32, p = 0.007, and HR = 2.61, 95% CI 1.01-6.74, p = 0.048, respectively). Other patient characteristics, blood test findings, irP severity, and response to prednisolone therapy were not associated with irP relapse. CONCLUSIONS: In irP patients treated with 6-week prednisolone tapering therapy, OP pattern and duration to irP onset ≥ 100 days were associated with relapse risk. Assessment of the risk factors for irP relapse will be helpful for irP management.

Improved vascular depiction and image quality through deep learning reconstruction of CT hepatic arteriography during transcatheter arterial chemoembolization.

PURPOSE: To evaluate the effect of deep learning reconstruction (DLR) on vascular depiction, tumor enhancement, and image quality of computed tomography hepatic arteriography (CTHA) images acquired during transcatheter arterial chemoembolization (TACE). METHODS: Institutional review board approval was obtained. Twenty-seven patients (18 men and 9 women, mean age, 75.7 years) who underwent CTHA immediately before TACE were enrolled. All images were reconstructed using three reconstruction algorithms: hybrid-iterative reconstruction (hybrid-IR), DLR with mild strength (DLR-M), and DLR with strong strength (DLR-S). Vascular depiction, tumor enhancement, feeder visualization, and image quality of CTHA were quantitatively and qualitatively assessed by two radiologists and compared between the three reconstruction algorithms. RESULTS: The mean signal-to-noise ratios (SNR) of sub-segmental arteries and sub-sub-segmental arteries, and the contrast-to-noise ratio (CNR) of tumors, were significantly higher on DLR-S than on DLR-M and hybrid-IR (P < 0.001). The mean qualitative score for sharpness of sub-segmental and sub-sub-segmental arteries was significantly better on DLR-S than on DLR-M and hybrid-IR (P < 0.001). There was no significant difference in the feeder artery detection rate of automated feeder artery detection software among three reconstruction algorithms (P = 0.102). The contrast, continuity, and confidence level of feeder artery detection was significantly better on DLR-S than on DLR-M (P = 0.013, 0.005, and 0.001) and hybrid-IR (P < 0.001, P = 0.002, and P < 0.001). The weighted kappa values between two readers for qualitative scores of feeder artery visualization were 0.807-0.874. The mean qualitative scores for sharpness, granulation, and diagnostic acceptability of CTHA were better on DLR-S than on DLR-M and hybrid-IR (P < 0.001). CONCLUSIONS: DLR significantly improved the SNR of small hepatic arteries, the CNR of tumor, and feeder artery visualization on CTHA images. DLR-S seems to be better suited to routine CTHA in TACE than does hybrid-IR.

Magnetic resonance imaging-based risk factors of hepatocellular carcinoma after direct-acting antiviral therapy: A multicenter observational study.

AIM: To determine risk factors associated with hepatocellular carcinoma (HCC) development following direct-acting antiviral (DAA) therapy. METHODS: We enrolled patients with chronic hepatitis C who underwent direct-acting antiviral therapy and achieved sustained virologic response at 12 weeks between 2012 and 2018. Subsequently, patients were followed up. The primary endpoint was the development of HCC or the date of the last follow up when the absence of HCC was confirmed. Uni- and multivariate Cox proportional hazards models were used to identify factors contributing to HCC development, including gadoxetic acid-enhanced magnetic resonance imaging findings. The cumulative incidence rates of HCC development were calculated using the Kaplan-Meier method, and differences between groups were assessed using the log-rank test. RESULTS: The final study cohort comprised 482 patients (median age 70.5 years; 242 men). The median follow-up period was 36.8 months. Among 482 patients, 96 developed HCC (19.9%). The 1-, 3-, and 5-year cumulative rates of HCC development were 4.9%, 18.6%, and 30.5%, respectively. Multivariate analysis revealed that age, male sex, history of HCC, and hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were independent risk factors significantly associated with HCC development (p < 0.001-0.04). The highest risk group included patients with both a history of HCC and the presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement (the 1- and 3-year cumulative HCC development rates were 14.2% and 62.2%, respectively). CONCLUSION: History of HCC and presence of hepatobiliary phase hypointense nodules without arterial phase hyperenhancement were strong risk factors for HCC development following direct-acting antiviral therapy.

Key CT and MRI findings of drug-associated hepatobiliary and pancreatic disorders.

Obtaining an imaging diagnosis of various hepatobiliary and pancreatic disorders caused by certain drugs can often be challenging. Familiarity with these conditions may improve diagnostic accuracy and patient management. This review aimed to describe the imaging findings of drug-associated hepatobiliary and pancreatic disorders and identify suggestions for obtaining a correct diagnosis. We focused on relatively common disorders or those that can present with characteristic imaging findings, such as drug-induced acute hepatitis, sinusoidal obstruction syndrome, focal nodular hyperplasia-like lesions, hepatocellular adenoma, pseudocirrhosis, chemotherapy-associated steatohepatitis, amiodarone deposition in the liver, secondary iron overload, drug-induced pancreatitis, pancreatic enlargement after epoprostenol therapy, ceftriaxone-associated gallbladder pseudolithiasis, immune-related adverse events, and methotrexate-associated lymphoproliferative disorders.

Fluorescein staining of chloroplast starch granules in living plants.

Chloroplast starch granules (cpSGs) store energy harvested through photosynthesis in plants, and cpSG dynamics have important roles in plant energy metabolism and stress responses. To date, cpSGs have been visualized using several methods, such as iodine staining; however, no method can be used to specifically visualize cpSGs in living cells from various plant species. Here, we report a simple method to visualize cpSGs in living plant cells in various species by staining with fluorescein, a commonly used fluorescent dye. We show that fluorescein is taken up into chloroplasts and interacts with cpSGs similarly to iodine. Fluorescein also interacts with refined starch in vitro. Using a fluorescein derivative for ultrabright cpSG imaging, we produced high-quality 3D reconstructions of cpSGs and evaluated their accumulation in multiple plant species. As fluorescein is well known and readily purchasable, our fluorescein-based staining method should contribute to all research regarding starch.

Association of the lung immune prognostic index with the survival of patients with idiopathic interstitial pneumonias.

BACKGROUND AND OBJECTIVE: The lung immune prognostic index (LIPI), a simple index calculated from the blood lactate dehydrogenase level and derived neutrophil-to-lymphocyte ratio, is thought to be associated with host immune status. However, the utility of LIPI in patients with idiopathic interstitial pneumonias (IIPs) is unknown. METHODS: In this multicentre, retrospective, observational study, an association between LIPI and the survival of patients with IIPs was evaluated. RESULTS: Exploratory and validation cohorts consisting of 460 and 414 patients with IIPs, respectively, were included (159 and 159 patients had idiopathic pulmonary fibrosis [IPF], and 301 and 255 had non-IPF, respectively). In the exploratory cohort, patients with IPF and a low LIPI had significantly better survival than those with a high LIPI (median of 5.6 years vs. 3.9 years, p = 0.016). The predictive ability of LIPI for the survival of patients with IPF was validated in the validation cohort (median of 8.5 years vs. 4.4 years, p = 0.003). In a multivariate Cox proportional hazard analysis, LIPI was selected as an independent predictive factor for the survival of IPF patients. There was no significant association between LIPI and survival of non-IPF patients in the exploratory and validation cohorts. CONCLUSION: The LIPI was a predictive factor for the survival of patients with IPF and could aid the management of IPF.

Gadoxetic Acid-Enhanced Liver MRI: Everything You Need to Know.

ABSTRACT: Since its introduction in the worldwide medical market, gadoxetic acid has attracted considerable interest. The year 2023 marks the 15th anniversary of the introduction of gadoxetic acid in Japan. Gadoxetic acid-enhanced magnetic resonance imaging (GA-MRI) is the predominantly performed contrast MRI examination for the liver. Its most essential characteristic, namely, the hepatobiliary phase, revolutionized the clinical management of liver disease. Gadoxetic acid-enhanced MRI is currently the most efficient method for focal liver lesion detection and analysis. Meta-analyses demonstrated its excellent effectiveness for the diagnosis of hepatocellular carcinoma and liver metastases. Owing to the extensive usage of gadoxetic acid, a hepatobiliary phase hypointense nodule without arterial phase hyperenhancement is well documented. The existence of such nodules may be a sign of hypervascular hepatocellular carcinoma in nodules and other areas in the liver. Apart from its role in tumor identification and characterization, GA-MRI can help assess response to therapy and liver fibrosis. Therefore, it is proposed to use gadoxetic acid as the first option for MRI of the liver in the majority of patients. The efficacy of gadoxetic acid surpasses its disadvantages, rendering this contrast agent the preferred choice for routine MRI of the liver. The clinical use of GA-MRI is discussed in this review article.

Six-week oral prednisolone therapy for immune-related pneumonitis: a single-arm phase II study.

BACKGROUND: There has been no prospective trial for treatment of immune-related pneumonitis (irP) occurred after immune checkpoint inhibitors (ICIs). METHODS: In this single-arm phase II study, patients with cancer with grade ≥2 irP received oral prednisolone (1 mg/kg/day), tapered over 6 weeks. The primary endpoint was a pneumonitis control rate at 6 weeks from the start of the study treatment, defined as complete disappearance or partial improvement of irP in high-resolution CT of the chest. RESULTS: Among 57 patients enrolled, 56 were included in the final analysis. The most frequent cause of irP was single ICI therapy (51.8%), followed by combination with chemotherapy plus ICI (39.3%). Thirty-five (62.5%) patients had grade 2 irP and 21 (37.5%) had grade ≥3. Fifty-one (91.1%) patients completed the study treatment while 5 discontinued the study treatment because of relapse of irP (n=1), death from cancer (n=1), occurrence of immune-related hepatitis (n=1), extension of the treatment duration more than 6 weeks (n=1), and attending physician's decision (n=1). Six weeks after the start of the study treatment, 16 (28.5%) patients demonstrated complete recovery from irP, 35 (62.5%) had a partial improvement in irP, 1 (1.8%) had a relapse of irP, and 4 (7.1%) were not evaluable. The pneumonitis control rate at 6 weeks was 91.1% (95% CI, 80.7% to 96.1%). Twelve weeks after the start of the study treatment, 5 (8.9%), 27 (48.2%), and 15 (26.8%) patients demonstrated complete recovery, partial improvement, and relapse, respectively, and 9 (16.1%) were not evaluable. The pneumonitis control rate at 12 weeks was 57.1% (95% CI, 44.1% to 69.2%). During the observation period, 18 (32.1%) patients experienced a relapse of irP, and of those, 17 received re-treatment with corticosteroids. Grade ≥3 adverse events occurred in 10 (17.9%) patients, in which hyperglycemia was most frequent (n=6). There was no treatment-related death. CONCLUSIONS: In this first prospective study for irP, prednisolone at 1 mg/kg/day, tapered over 6 weeks, demonstrated a promising clinical benefit and manageable toxicity, suggesting a potential treatment option for irP. TRIAL REGISTRATION NUMBER: jRCT: 1041190029.

Inter-observer agreement and accuracy of LI-RADS v2018 for differentiating tumor in vein from bland thrombus using gadoxetic acid-enhanced magnetic resonance imaging.

PURPOSE: To assess inter-observer agreement and accuracy of LI-RADS v2018 for differentiating tumor in vein (TIV) from bland thrombus on gadoxetic acid-enhanced magnetic resonance imaging (Gx-MRI). Secondarily, to determine whether a multi-feature model improves accuracy compared to LI-RADS. METHODS: We retrospectively identified consecutive patients at risk for hepatocellular carcinoma with venous occlusion(s) reported on Gx-MRI. Five radiologists independently classified each occlusion as TIV or bland thrombus using the LI-RADS TIV criterion (enhancing soft tissue in vein). They also evaluated imaging features suggestive of TIV or bland thrombus. Intra-class correlation coefficient (ICC) was calculated for individual features. A multi-feature model was developed based on consensus scores of features with > 5% consensus prevalence and > 0.40 ICC. Sensitivity and specificity of the LI-RADS criterion and of the cross-validated multi-feature model were compared. RESULTS: Ninety-eight patients with 103 venous occlusions (58 TIV, 45 bland thrombus) were included. The LI-RADS criterion provided 0.63 ICC and, depending on the reader, 0.62-0.93 sensitivity and 0.87-1.00 specificity. Five other features had > 5% consensus prevalence and > 0.40 ICC, including three LI-RADS suggestive features and two non-LI-RADS features. The optimal multi-feature model incorporated the LI-RADS criterion and one LI-RADS suggestive feature (occluded or obscured vein contiguous with malignant parenchymal mass). After cross-validation, the multi-feature model did not improve sensitivity or specificity compared to the LI-RADS criterion (P = 0.23 and 0.25, respectively). CONCLUSION: Using Gx-MRI, the LI-RADS criterion for TIV provides substantial inter-observer agreement, variable sensitivity, and high specificity for differentiating TIV from bland thrombus. A cross-validated multi-feature model did not improve diagnostic performance.

Clinical Significance of Liver MR Imaging.

MRI is widely used in clinical practice for detecting liver diseases. Since the introduction of gadoxetic acid, MRI has become the most effective modality for the detection and characterization of focal liver lesions. According to previous meta-analyses, the area under the receiver operating characteristic curve (AUROC) was 0.97-0.99 for the diagnosis of small hepatocellular carcinoma (≥ 2 cm) by gadoxetic-acid-enhanced MRI. Moreover, the AUROC for the diagnosis of colorectal liver metastases was significantly high (0.98). Despite gadoxetic acid's drawbacks, its clinical utility outweighs them, making it the contrast agent of choice in routine liver MRIs. Moreover, clinically, liver MRI has become more prevalent for a quantitative assessment. Liver fibrosis can be evaluated using MR elastography; whereas, hepatic steatosis and iron overload can be evaluated using proton density fat fraction, with high accuracy and reproducibility. This article reviewed the usefulness of liver MRI, which can be a comprehensive imaging modality in clinical practice.

A predictive model for acute exacerbation of idiopathic interstitial pneumonias.

BACKGROUND: Acute exacerbation of idiopathic interstitial pneumonias (AE-IIPs) induces permanent pulmonary dysfunction and is potentially lethal. The unpredictable occurrence of AE-IIPs remains an important clinical issue in the management of IIPs. METHODS: In this multicentre, retrospective, observational study, a predictive score for AE-IIPs was designed using clinical factors based on multivariate Fine-Gray analysis in patients with IIPs. RESULTS: Based on multivariate Fine-Gray analysis in an exploratory cohort of 487 patients with IIPs, the predictive score for AE-IIPs was determined as follows: 1 point each was added for honeycombing on high-resolution computed tomography (H), age >75 years (A) and lactate dehydrogenase level >222 U·L-1 (L); the total score ranged from 0 to 3 (HAL score). The HAL score discriminated the risk of AE-IIPs with a C-index of 0.62 (95% CI 0.56-0.67); this discrimination was verified in a validation cohort of 402 patients with IIPs with a C-index of 0.67 (95% CI 0.60-0.73). In a combined cohort, the estimated cumulative risks for AE-IIPs at 1, 2, 3, 5 and 10 years were 1.9%, 3.5%, 5.1%, 7.7% and 12.9%, respectively, in the total score 0 group; 4.7%, 8.3%, 12.0%, 17.7% and 28.4%, respectively, in the total score 1 group; and 8.0%, 14.2%, 19.7%, 28.7% and 43.0%, respectively, in the total score ≥2 group. Subgroup analysis revealed that the HAL score was applicable to patients with and without idiopathic pulmonary fibrosis. CONCLUSIONS: The HAL score discriminated the risk of AE-IIPs and could aid in the management of IIPs.

Diagnostic value of heart-to-mediastinum ratio in 99mTc-pyrophospate SPECT/CT for transthyretin cardiac amyloidosis.

BACKGROUND: In transthyretin cardiac amyloidosis (ATTR-CA), 99mTc-pyrophosphate myocardial scintigraphy (99mTc-PYP) is a diagnostic tool that utilizes visual and quantitative evaluation. However, false positive cases can occur because of tracer accumulation in the blood. We investigated the effectiveness of the heart-to-mediastinum (H/M) ratio of 99mTc-PYP in ATTR-CA diagnosis. METHODS: We retrospectively included 164 patients who underwent 99mTc-PYP single-photon emission computed tomography/computed tomography between March 2019 and January 2022. The diagnostic accuracy of ATTR-CA was examined by the heart-to-contralateral lung (H/CL) and H/M ratio calculated at 3 hours post-tracer administration. RESULTS: After the exclusion of patients who did not undergo endomyocardial biopsy, 30 patients (15 each with ATTR-CA and without ATTR-CA) were included. The receiver operating characteristic curve used to distinguish ATTR-CA from non-ATTR-CA patients revealed an area under the curve of 0.986 and 0.943, respectively. A H/M ratio of > 1.41 identified ATTR-CA patients with a sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 100, 93.3, 93.3, and 100%, respectively. Conversely, an H/CL ratio of > 1.3 identified ATTR-CA patients with 100% sensitivity, 40.0% specificity, 62.5% PPV, and 100% NPV. CONCLUSION: The H/M ratio obtained at 3 hours post-injection has the potential to be a novel indicator for ATTR-CA.

Model-based Deep Learning Reconstruction Using a Folded Image Training Strategy for Abdominal 3D T1-weighted Imaging.

PURPOSE: To evaluate the feasibility of folded image training strategy (FITS) and the quality of images reconstructed using the improved model-based deep learning (iMoDL) network trained with FITS (FITS-iMoDL) for abdominal MR imaging. METHODS: This retrospective study included abdominal 3D T1-weighted images of 122 patients. In the experimental analyses, peak SNR (PSNR) and structure similarity index (SSIM) of images reconstructed with FITS-iMoDL were compared with those with the following reconstruction methods: conventional model-based deep learning (conv-MoDL), MoDL trained with FITS (FITS-MoDL), total variation regularized compressed sensing (CS), and parallel imaging (CG-SENSE). In the clinical analysis, SNR and image contrast were measured on the reference, FITS-iMoDL, and CS images. Three radiologists evaluated the image quality using a 5-point scale to determine the mean opinion score (MOS). RESULTS: The PSNR of FITS-iMoDL was significantly higher than that of FITS-MoDL, conv-MoDL, CS, and CG-SENSE (P < 0.001). The SSIM of FITS-iMoDL was significantly higher than those of the others (P < 0.001), except for FITS-MoDL (P = 0.056). In the clinical analysis, the SNR of FITS-iMoDL was significantly higher than that of the reference and CS (P < 0.0001). Image contrast was equivalent within an equivalence margin of 10% among these three image sets (P < 0.0001). MOS was significantly improved in FITS-iMoDL (P < 0.001) compared with CS images in terms of liver edge and vessels conspicuity, lesion depiction, artifacts, blurring, and overall image quality. CONCLUSION: The proposed method, FITS-iMoDL, allowed a deeper MoDL reconstruction network without increasing memory consumption and improved image quality on abdominal 3D T1-weighted imaging compared with CS images.

An Intra-individual Comparison between Free-breathing Dynamic MR Imaging of the Liver Using Stack-of-stars Acquisition and the Breath-holding Method Using Cartesian Sampling or View-sharing.

PURPOSE: To compare the quality of dynamic imaging between stack-of-stars acquisition without breath-holding (DISCO-Star) and the breath-holding method (Cartesian LAVA and DISCO). METHODS: This retrospective study was conducted between October 2019 and February 2020. Two radiologists performed visual assessments of respiratory motion or pulsation artifacts, streak artifacts, liver edge sharpness, and overall image quality using a 5-point scale for two datasets: Dataset 1 (n = 107), patients with Cartesian LAVA and DISCO-Star; Dataset 2 (n = 41), patients with DISCO and DISCO-Star at different time points. Diagnosable image quality was defined as ≥ 3 points in overall image quality. Whether the scan timing of the arterial phase (AP) was appropriate was evaluated, and results between the pulse sequences were compared. In cases of inappropriate scan timing in the DISCO-Star group, retrospective reconstruction with a high frame rate (80 phases, 3 s/phase) was added. RESULTS: The overall image quality of Cartesian LAVA was better than that of DISCO-Star in AP. However, noninferiority was shown in the ratio of diagnosable images between Cartesian LAVA and DISCO-Star in AP. There was no significant difference in the ratio of appropriate scan timing between DISCO-Star and Cartesian LAVA; however, the ratio of appropriate scan timing in DISCO-Star with high frame rate reconstruction was significantly higher than that in Cartesian LAVA in both readers. Overall image quality scores between DISCO and DISCO-Star were not significantly different in AP. There was no significant difference in the ratio of appropriate scan timing between DISCO-Star with high frame rate reconstruction and DISCO in both readers. CONCLUSION: The use of DISCO-Star with high frame rate reconstruction is a good solution to obtain appropriate AP scan timing compared with Cartesian LAVA. DISCO-Star showed equivalent image quality in all phases and in the ratio of appropriate AP scan timing compared with DISCO.

Live-cell imaging of the chloroplast outer envelope membrane using fluorescent dyes.

Chloroplasts are organelles composed of sub-organellar compartments-stroma, thylakoids, and starch granules-and are surrounded by outer and inner envelope membranes (OEM and IEM, respectively). The chloroplast OEM and IEM play key roles not only as a barrier separating the chloroplast components from the cytosol but also in the interchange of numerous metabolites and proteins between the chloroplast interior and the cytosol. Fluorescent protein markers for the chloroplast OEM have been widely used to visualize the outermost border of chloroplasts. However, the use of marker proteins requires an established cellular genetic transformation method, which limits the plant species in which marker proteins can be used. Moreover, the high accumulation of OEM marker proteins often elicits abnormal morphological phenotypes of the OEM. Because the OEM can currently only be visualized using exogenous marker proteins, the behaviors of the chloroplast and/or its OEM remain unknown in wild-type cells of various plant species. Here, we visualized the OEM using live-cell staining with the fluorescent dyes rhodamine B and Nile red in several plant species, including crops. We propose rhodamine B and Nile red as new tools for visualizing the chloroplast OEM in living plant cells that do not require genetic transformation. Significance Statement: We established a live-cell imaging method to visualize the chloroplast outer envelope membrane by staining living cells with fluorescent dyes. This method does not require genetic transformation and allows the observation of the chloroplast outer envelope membrane in various plant species.

Non-traumatic adult acute abdomen with high-attenuation lesions or materials in the gastrointestinal tract on unenhanced computed tomography.

Computed tomography (CT) is an imaging modality that provides otherwise unobtainable information in the diagnostic workup for acute abdomen. The patient's clinical history, physical examination, and laboratory findings are essential for a correct diagnosis; however, some diagnoses are difficult to establish. Although contrast-enhanced CT is the preferred diagnostic tool and provides invaluable information, using only post-contrast images can lead to misdiagnoses. Unenhanced CT images are more useful than post-contrast images for detecting high-attenuation lesions or materials because surrounding tissues also show high attenuation on post-contrast images. Unenhanced CT often provides key imaging findings for a correct diagnosis; hence, the purpose of this article is to describe CT findings in acute abdomen with high-attenuation lesions in the gastrointestinal tract.

Organellar Glue: A Molecular Tool to Artificially Control Chloroplast-Chloroplast Interactions.

Organelles can physically interact to facilitate various cellular processes such as metabolite exchange. Artificially regulating these interactions represents a promising approach for synthetic biology. Here, we artificially controlled chloroplast-chloroplast interactions in living plant cells with our organelle glue (ORGL) technique, which is based on reconstitution of a split fluorescent protein. We simultaneously targeted N-terminal and C-terminal fragments of a fluorescent protein to the chloroplast outer envelope membrane or cytosol, respectively, which induced chloroplast-chloroplast interactions. The cytosolic C-terminal fragment likely functions as a bridge between two N-terminal fragments, thereby bringing the chloroplasts in close proximity to interact. We modulated the frequency of chloroplast-chloroplast interactions by altering the ratio of N- and C-terminal fragments. We conclude that the ORGL technique can successfully control chloroplast-chloroplast interactions in plants, providing a proof of concept for the artificial regulation of organelle interactions in living cells.