Generation of footprint-free, high-quality feline induced pluripotent stem cells using Sendai virus vector.

Companion animals, such as felines and canines, could provide an excellent platform for translational research from veterinary to human medicine. However, the use of feline induced pluripotent stems (fiPSCs) of quality in basic or clinical research has not been reported. Here, we generated footprint-free fiPSCs derived from embryonic cells, as well as juvenile feline uterus-derived cells using Sendai virus vector harboring six feline-specific pluripotency-associated genes. The fiPSCs were confirmed to be of high quality with the potential to form teratomas including all three germ layers. Furthermore, our fiPSCs were maintained under feeder-free and chemically-defined conditions using StemFit® AK02N and recombinant laminin 511, iMatrix-511. Further research on fiPSCs could result in their widespread application in veterinary regenerative medicine, which could pave the way for their use in advanced regenerative medicine research for humans.

Bi-layered Adipose Mesenchymal Cell Sheets Improve Bladder Compliance in Spinal Cord-Injured Rats.

To improve bladder compliance in patients with low-compliance bladders, augmentation cystoplasty with the intestinal tract is performed. However, the use of the intestinal tract often leads to serious surgical complications. Tissue engineering technologies have the potential to improve bladder compliance without using the intestinal tract. In this study, we fabricated bi-layered adipose-derived mesenchymal cell (AMC) sheets and then determined whether the bi-layered AMC sheets could improve bladder compliance in rats with spinal cord injury (SCI). The abdominal adipose tissues of green fluorescence protein (GFP)-transfected Sprague-Dawley (SD) rats were harvested, and the attached and proliferating cells on type I collagen were used as AMCs. The AMCs were then cultured on temperature-responsive culture dishes. After reaching over-confluence, the AMCs that maintained cell-cell contacts were detached from the dishes and applied to a gelatin hydrogel sheet. Then, another detached AMC monolayer was accumulated on the AMC monolayer-applied gelatin. Prior to 4 weeks of transplantation, the levels of T8-9 in the spinal cords of recipient SD rats were partially transected. After producing the bi-layered AMC sheets and the rats with SCI, the detrusor muscles of the anterior bladder walls of the rats with SCI were incised, and the bi-layered AMC sheet was patch-transplanted onto the exposed bladder epithelium (n = 8). As a control, the sham operation was performed (n = 7). Four weeks after the transplantation, bladder capacity and bladder compliance in AMC sheet-transplanted SCI rats were significantly higher than those in sham-operated control SCI rats. The smooth muscle layers in AMC sheet-transplanted bladders were significantly larger than those in control bladders. In addition, the collagen fibers in the AMC sheet-transplanted bladders were significantly smaller than those in the control bladders. Some GFP-positive transplanted AMCs differentiated into smooth muscle actin- or desmin-positive cells. Furthermore, GFP-positive cells secreted transforming growth factor-ß1 or vascular endothelial growth factor. Therefore, this study showed that bi-layered AMC sheets could improve bladder compliance and bladder tissues in SCI rats.

One-Month Dual Antiplatelet Therapy Followed by P2Y12 Inhibitor Monotherapy After Biodegradable Polymer Drug-Eluting Stent Implantation　- The REIWA Region-Wide Registry.

BACKGROUND: The safety and feasibility of using 1-month dual antiplatelet therapy (DAPT) followed by P2Y12inhibitor monotherapy for patients after percutaneous coronary intervention (PCI) with thin-strut biodegradable polymer drug-eluting stents (BP-DES) in daily clinical practice remain uncertain. METHODS AND RESULTS: The REIWA region-wide registry is a prospective study conducted in 1 PCI center and 9 local hospitals in northern Japan. A total of 1,202 patients who successfully underwent final PCI using BP-DES (Synergy: n=400; Ultimaster: n=401; Orsiro: n=401), were enrolled in the registry, and received 1-month DAPT followed by P2Y12inhibitor (prasugrel 3.75 mg/day or clopidogrel 75 mg/day) monotherapy. The primary endpoint was a composite of cardiovascular and bleeding events at 12 months, including cardiovascular death, myocardial infarction (MI), definite stent thrombosis (ST), ischemic or hemorrhagic stroke, and Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding. Based on the results of a previous study, we set the performance goal at 5.0%. Over the 1-year follow-up, the primary endpoint occurred in 3.08% of patients, which was lower than the predefined performance goal (Pnon-inferiority<0.0001). Notably, definite ST occurred in only 1 patient (0.08%) within 1 year (at 258 days). No differences were observed in the primary endpoint between stent types. CONCLUSIONS: The REIWA region-wide registry suggests that 1-month DAPT followed by P2Y12inhibitor monotherapy is safe and feasible for Japanese patients with BP-DES.

Analyses of mRNA Expression Levels of Pituitary Hormones, Their Hypothalamic Regulating Factors, and Receptors Involved in Metamorphosis with Special Reference to the Summer and Winter Seasons.

Bullfrog (Rana catesbeiana) larvae inhabiting the main island of Japan overwinter as preclimax animals, whereas the larvae that reached climax in summer complete metamorphosis. We analyzed the mRNA expression levels of the adenohypophyseal hormones, hypothalamic hormones, and their receptors that are involved in controlling metamorphosis in tadpoles at various developmental stages available in summer and winter in order to understand the hormonal mechanism regulating metamorphosis progression. Corticotropin-releasing factor (CRF) and thyrotropin ß-subunit (TSHß) mRNA expression was enhanced as they reached the climax stage in metamorphosing summer tadpoles, although type 2 CRF receptor (CRFR2) mRNA levels demonstrated a tendency of elevation, indicating the activation of the hypothalamo-hypophyseal axis for stimulating the release of thyroid hormone in summer. Arginine vasotocin (AVT) mRNA levels were elevated as metamorphosis progressed, but mRNA expression levels were not synchronized with those of proopiomelanocortin (POMC) and V1b-type AVT receptor (V1bR). The elevation of mRNA levels of prolactin (PRL) 1A and type 3 thyrotropin-releasing hormone receptor (TRHR3), but not of thyrotropin-releasing hormone (TRH) precursor mRNA levels, was noted in climactic tadpoles, indicating that PRL mRNA levels are not simply dependent on the expression levels of TRH precursor mRNA. In the preclimactic larvae captured in winter, which are in metamorphic stasis, mRNA levels of pituitary hormones, hypothalamic factors, and their receptors remained low or at levels similar to those of the larvae captured in summer. These results indicate the relationship between the mRNA expression of metamorphosis-related factors and the seasonal progression/stasis of metamorphosis.

Comparisons of in-hospital fee and surgical outcomes between robot-assisted, laparoscopic, and open radical cystectomy: a Japanese nationwide study.

OBJECTIVE: To evaluate in-hospital fees and surgical outcomes of robot-assisted radical cystectomy (RARC), laparoscopic radical cystectomy (LRC) and open radical cystectomy (ORC) using a Japanese nationwide database. METHODS: All data were obtained from the Diagnosis Procedure Combination database between April 2020 and March 2022. Basic characteristics and perioperative indicators, including in-hospital fees, were compared among the RARC, LRC and ORC groups. Propensity score-matched comparisons were performed to assess the differences between RARC and ORC. RESULTS: During the study period, 2931, 1311 and 2435 cases of RARC, LRC and ORC were identified, respectively. The RARC group had the lowest in-hospital fee (median: 2.38 million yen), the shortest hospital stay (26 days) and the lowest blood transfusion rate (29.5%), as well as the lowest complication rate (20.9%), despite having the longest anesthesia time (569 min) among the three groups (all P < 0.01). The outcomes of LRC were comparable with those of RARC, and the differences in these indicators between the RARC and ORC groups were greater than those between the RARC and LRC groups. In propensity score-matched comparisons between the RARC and ORC groups, the differences in the indicators remained significant (all P < 0.01), with an ~50 000 yen difference in in-hospital fees. CONCLUSIONS: RARC and LRC were considered to be more cost-effective surgeries than ORC due to their superior surgical outcomes and comparable surgical fees in Japan. The widespread adoption of RARC and LRC is expected to bring economic benefits to Japanese society.

Urinary tract infection associated with bacteremia caused by vancomycin-resistant enterococcus following continent urinary diversion.

Key Clinical Message: Even in a country where vancomycin-resistant enterococcus is rare, multidrug-resistant organism precautions are necessary when admitting patients with a history of medical exposure in other countries. On admission, screening is necessary and if infection is confirmed, a multidisciplinary approach involving different specialists is required. Abstract: The patient was a 49-year-old Japanese female living in the United States. Total pelvic exenteration for cervical carcinoma, Miami pouch formation, and ileostomy had been performed in the United States. She returned to Japan to undergo postoperative adjuvant chemotherapy. Fever and abdominal pain occurred 42 days after surgery. She consulted the fever outpatient clinic, and a diagnosis of urinary retention-associated acute renal failure and pyelonephritis was made. We detected vancomycin-resistant enterococcus on urine/blood culture 5 days after admission. Infection control measures were implemented, and the ward was closed for 3 days. We administered linezolid, which was effective for pyelonephritis and bacteremia.

Fucoidan from brown seaweed Tubinaria decurrens: Structure and structure - anticancer activity relationship.

The aims of this study are to determine the structure of a fucoidan from brown seaweed Turbinaria decurrens, to investigate its anticancer activity and structure-activity relationship. SEC-MALLS, IR, ESI-MS and NMR spectra analysis indicated that dominant structure of the fucoidan, with a Mw 122.6 KDa, has a backbone of (1 â†’ 3)- and (1 â†’ 4)-α-L-Fucp residues, branched at C-4, sulfate groups are attached at C-2, C-3 and C-4; branches are (1 â†’ 4)-ß-D-Galp residues and sulfated at C-2. The fucoidan was hydrolyzed by HCl aqueous solution to obtain hydrolyzed fucoidans. It is assumed that native and hydrolyzed fucoidans have a rod-like conformation in solution with cross-sectional radius of gyration (Rgc) ranged from 0.53 to 1.52 nm as estimated from SAXS measurements. The fucoidans show great anticancer activity against HT29 human colon cancer cell line with IC50 ranging from 5.41 ± 0.36 to 73.52 ± 2.54 µg/mL. Anticancer activity of the fucoidan could be significantly improved by lowering molecular weight, furthermore, fucoidan required small molecular weight, small molecular weight distribution and rod-like structure with a short branch length for high anticancer activity.

Use of genome-wide DNA methylation analysis to identify prognostic CpG site markers associated with longer survival time in dogs with multicentric high-grade B-cell lymphoma.

BACKGROUND: DNA methylation analysis might identify prognostic CpG sites in CHOP-treated dogs with multicentric high-grade B-cell lymphoma (MHGL) with heterogenous prognosis. OBJECTIVE: To identify prognostic CpG sites of MHGL through genome-wide DNA methylation analysis with pyrosequencing validation. ANIMALS: Test group: 24 dogs. Validation group: 100 dogs. All client-owned dogs were diagnosed with MHGL and treated with CHOP chemotherapy. METHODS: Cohort study. DNA was extracted from lymph node samples obtained via FNA. Genome-wide DNA methylation analysis using Digital Restriction Enzyme Analysis of Methylation (DREAM) was performed on the test group to identify differentially methylated CpG sites (DMCs). Bisulfite pyrosequencing was used to measure methylation status of candidate DMCs in the validation group. Median survival times (MST) were analyzed using Kaplan-Meier (log-rank) product limit method. RESULTS: DREAM analyzed 101 576 CpG sites. Hierarchical clustering of 16 262 CpG sites in test group identified group with better prognosis (MST = 55-477 days vs 10-301 days, P = .007). Volcano plot identified 1371 differentially methylated CpG sites (DMCs). DMC near the genes of FAM213A (DMC-F) and PHLPP1 (DMC-P) were selected as candidates. Bisulfite-pyrosequencing performed on validation group showed group with methylation level of DMC-F < 40% had favorable prognosis (MST = 11-1072 days vs 8-1792 days, P = .01), whereas group with the methylation level combination of DMC-F < 40% plus DMC-P < 10% had excellent prognosis (MST = 18-1072 days vs 8-1792 days, P = .009). CONCLUSION AND CLINICAL IMPORTANCE: Methylation status of prognostic CpG sites delineate canine MGHL cases with longer MST, providing owners with information on expectations of potential improved treatment outcomes.

Intranodal glue embolization for lymphorrhea following inguinal lymphadenectomy in penile cancer: A case report.

An 86-year-old man underwent total penectomy and bilateral inguinal lymphadenectomy (ILND) for penile cancer with an enlarged right inguinal lymph node. The accumulation of 100-150 ml of lymphatic fluid was observed in the right inguinal drain in a day after surgery. Compression was performed, without any improvement in lymphorrhea. During the right inguinal lymphangiography performed on postoperative day (POD) 28, lymphorrhea was still detected. Lymphorrhea was improved 2 days after intranodal glue embolization (IGE) was performed using a mixture of lipiodol and n-butyl-2 cyanoacrylate (NBCA). IGE was effective for intractable lymphorrhea after ILND in penile cancer.

Hypoxia and lactate influence VOC production in A549 lung cancer cells.

Introduction: Cancer cells emit characteristic volatile organic compounds (VOCs), which are potentially generated from ROS-based lipid peroxidation of polyunsaturated fatty acids. The metabolism of such VOCs and their regulation remain to be fully investigated. In fact, the enzymes involved in the synthesis of these VOCs have not been described yet. Methods: In this study, we firstly conducted in vitro enzyme assays and demonstrated that recombinant alcohol dehydrogenase (ADH) converted Trans 2-hexenal into Trans 2-hexenol. The latter has previously been reported as a cancer VOC. To study VOC metabolism, 14 different culture conditions were compared in view of Trans 2-hexenol production. Results and discussion: The data indicate that hypoxia and the addition of lactate positively influenced Trans 2-hexenol production in A549 cancer cells. The RNAseq data suggested certain gene expressions in the VOC pathway and in lactate signaling, parallel to VOC production. This implies that hypoxia and lactate signaling with a VOC production can be characteristic for cancer in vitro.

Correlation between Respiratory Dysfunction and Dysphagia in Individuals with Acute Traumatic Cervical Spinal Cord Injury.

Introduction: Aspiration pneumonia is one of the most frequent and fatal life-threatening complications among individuals with acute traumatic cervical spinal cord injury (CSCI). However, the mechanism of dysphagia among individuals with CSCI is not well understood. Morbidity and mortality associated with CSCI may result from the interplay between respiratory dysfunction and dysphagia. This study aimed to elucidate the effect of respiratory dysfunction on the swallowing function of individuals with acute traumatic CSCI. Methods: A prospective cohort study was conducted involving 54 individuals with acute traumatic CSCI who were admitted within 2 weeks following injury. Dysphagia was evaluated using the Dysphagia Severity Scale (DSS) and the Functional Oral Intake Scale (FOIS). Respiratory function was evaluated by measuring the cough peak flow (CPF), forced expiratory volume in 1 s (FEV1.0), FEV1.0/forced vital capacity (FEV1.0%), and percent vital capacity (%VC). We recorded these parameters at weeks 2, 4, 8, and 12 following injury and analyzed pertinent changes over time and significant correlations. Results: Among 54 individuals (46 men and 8 women) recruited in this study, 48 (88.9%) had restrictive ventilatory impairment and 17 (31.5%) had severe dysphagia (DSS level 1-4) 2 weeks following injury. However, respiratory function and swallowing function significantly improved thereafter. CPF, FEV1.0, and %VC were significantly correlated with the severity of dysphagia during each period. Conclusions: Restrictive ventilatory impairment, poor cough force, and dysphagia are closely related, and the evaluation of respiratory function plays an important role in evaluating dysphagia.

Large-scale epidemiological study on feline autosomal dominant polycystic kidney disease and identification of novel PKD1 gene variants.

OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is a common inherited disease in cats. In most cases, the responsible abnormality is a nonsense single nucleotide polymorphism in exon 29 of the PKD1 gene (chrE3:g.42858112C>A, the conventional PKD1 variant). The aim of this study was to conduct a large-scale epidemiological study of ADPKD caused by the conventional PKD1 variant in Japan and to search for novel polymorphisms by targeted resequencing of the PKD1 using a next-generation sequencer. METHODS: A total of 1281 cats visiting the Veterinary Medical Center of the University of Tokyo were included in this study. DNA was extracted from the blood of each cat. We established a novel TaqMan real-time PCR genotyping assay for the conventional PKD1 variant, and all cases were examined for the presence of this variant. Targeted resequencing of all exons of the PKD1 was performed on the DNA of 23 cats with the conventional PKD1 variant, six cats diagnosed with cystic kidneys but without this variant, and 61 wild-type normal cats. RESULTS: Among the 1281 cats examined in this study, 23 (1.8%) harboured the conventional PKD1 variant. The odds of having the conventional PKD1 variant were significantly higher in Persian cats, Scottish Folds and Exotic Shorthairs than in the other breeds, although the number of cases in each breed was small. Furthermore, we identified four variants unique to cats with cystic kidneys that were not found in wild-type normal cats, all of which were in exon 15. In particular, two (chrE:g.42848725delC, pGly1641fs and chrE:g.42850283C>T, pArg2162Trp) were candidate variants. CONCLUSIONS AND RELEVANCE: This study revealed that the conventional PKD1 variant was prevalent in Scottish Fold, Persian and Exotic Shorthair breeds in Japan, and variants in exon 15 of PKD1, in addition to the conventional variant in exon 29, would be key factors in the pathogenesis of ADPKD in cats.

Whole exome and transcriptome analysis revealed the activation of ERK and Akt signaling pathway in canine histiocytic sarcoma.

Histiocytic sarcoma (HS) is an incurable aggressive tumor, and no consensus has been made on the treatment due to its rare occurrence. Since dogs spontaneously develop the disease and several cell lines are available, they have been advocated as translational animal models. In the present study, therefore, we explored gene mutations and aberrant molecular pathways in canine HS by next generation sequencing to identify molecular targets for treatment. Whole exome sequencing and RNA-sequencing revealed gene mutations related to receptor tyrosine kinase pathways and activation of ERK1/2, PI3K-AKT, and STAT3 pathways. Analysis by quantitative PCR and immunohistochemistry revealed that fibroblast growth factor receptor 1 (FGFR1) is over-expressed. Moreover, activation of ERK and Akt signaling were confirmed in all HS cell lines, and FGFR1 inhibitors showed dose-dependent growth inhibitory effects in two of the twelve canine HS cell lines. The findings obtained in the present study indicated that ERK and Akt signaling were activated in canine HS and drugs targeting FGFR1 might be effective in part of the cases. The present study provides translational evidence that leads to establishment of novel therapeutic strategies targeting ERK and Akt signaling in HS patients.

Toxic epidermal necrolysis after the administration of enfortumab vedotin for urinary bladder urothelial carcinoma.

Introduction: Enfortumab vedotin is a novel drug for locally advanced or metastatic urothelial carcinoma, but it is associated with a high incidence of skin reactions (up to 47.0%). Case presentation: A 71-year-old male was administered enfortumab vedotin for bladder cancer associated with lymph node metastases. Slight erythema of the upper limbs appeared on Day 5. Erythema gradually worsened. On Day 8, second administration was performed. On Day 12, based on the extents of blisters, erosion, and epidermolysis, a diagnosis of toxic epidermal necrolysis was made. The patient died of multiple organ failure on Day 18. Conclusion: As serious cutaneous toxicity may appear early after the start of administration, it is important to consider the timing of the second administration of the initial course carefully. In cases of skin reaction, reduction or discontinuation should be considered.

ALBI Grade Is a Predictive Factor of Lenvatinib Treatment Discontinuation due to Adverse Events in Hepatocellular Carcinoma.

BACKGROUND/AIM: Lenvatinib is a multiple-tyrosine kinase inhibitor used to treat hepatocellular carcinoma (HCC), and its systematic concentration varies according to liver function. The albumin-bilirubin (ALBI) grade is a novel indicator for predicting liver function in patients with hepatic disease. This study aimed to investigate the relationship between ALBI grade and HCC patients' lenvatinib treatment duration. PATIENTS AND METHODS: This is a retrospective cohort study of patients with HCC and Child-Pugh A treated with lenvatinib between April 2018 and December 2019. The baseline liver function was determined using the ALBI grade. The primary outcome was discontinuation owing to adverse events. The risk factors for discontinuation owing to adverse effects were analyzed using logistic regression. RESULTS: This investigation included 48 HCC patients. Patients with ALBI grade 2 had a significantly shorter time of discontinuation due to adverse events than those with grade 1 (p=0.036). However, the time of treatment failure did not differ between the groups. Multiple logistic regression analysis showed that ALBI grade 2 and non-use of antihypertensive drugs were independent factors for discontinuation due to adverse events [odds ratio (OR)=14.1, 95% confidence interval (CI)=1.46-135, p=0.022 and OR=5.48, 95% CI=1.13-23.9, p=0.024, respectively]. CONCLUSION: The ALBI grades may be useful in predicting adverse events caused by lenvatinib in patients with HCC and Child-Pugh A.

Correlation between the Biodistribution of Bovine Leukemia Virus in the Organs and the Proviral Load in the Peripheral Blood during Early Stages of Experimentally Infected Cattle.

Bovine leukemia virus (BLV) is the etiological agent of enzootic bovine leukosis. However, the propagation and distribution of BLV after primary infection still need to be fully elucidated. Here, we experimentally infected seven cattle with BLV and analyzed the BLV proviral load (PVL) in the blood and various organs. BLV was first detected in the blood of the cattle after one week, and the blood PVL increased for three weeks after infection. The PVL was maintained at a high level in five cattle, while it decreased to a low or medium level in two cattle. BLV was distributed in various organs, such as the heart, lung, liver, kidney, abomasum, and thymus, and, notably, in the spleen and lymph nodes. In cattle with a high blood PVL, BLV was detected in organs other than the spleen and lymph nodes, whereas in those with a low blood PVL, BLV was only detected in the spleen and lymph nodes. The amount of BLV in the organs was comparable to that in the blood. Our findings point to the possibility of estimating the distribution of BLV provirus in organs, lymph nodes, and body fluids by measuring the blood PVL, as it was positively correlated with the biodistribution of BLV provirus in the body of BLV infection during early stages.

[EXPERIENCES OF CONTACT LASER VAPORIZATION OF THE PROSTATE (CVP) FOR TREATING BENIGN PROSTATIC HYPERPLASIA IN THE LOCAL HOSPITAL].

(Objective) We started contact laser vaporization of the prostate (CVP) for treating benign prostatic hyperplasia at our hospital in July 2019. Forty-five patients were treated with CVP from July 2019 to April 2021. (Methods) Patients were assessed preoperatively and at one and three months after CVP treatment by using the International Prostate Symptom Score (IPSS), quality of life index (QOL index), peak urinary flow rate (Qmax), and postvoid residual urine volume (PVR). (Results) IPSS, QOL index, Qmax, and PVR significantly improved three months after CVP (p<0.05). Regarding adverse events, five patients developed early external urinary meatus strictures, two had postoperative bleeding, and three had temporary urinary retention. (Conclusions) In our hospital, elderly patients and patients who cannot discontinue an antithrombotic drug were treated by CVP for benign prostatic hyperplasia relatively safely.

Characterisation of canine CD34+/CD45 diminished cells by colony-forming unit assay and transcriptome analysis.

Haematopoietic stem and progenitor cells (HSPCs) are used for transplantation to reconstruct the haematopoietic pathways in humans receiving severe chemotherapy. However, the characteristics of canine HSPCs, such as specific surface antigens and gene expression profiles, are still unclear. This study aimed to characterise the haematopoietic ability and gene expression profiles of canine bone marrow HSPCs in healthy dogs. In this study, the CD34 positive (CD34+) cells were defined as classical HSPCs, CD34+/CD45 diminished (CD45dim) cells as more enriched HSPCs, and whole viable cells as controls. Haematopoietic abilities and gene expression profiles were evaluated using a colony-forming unit assay and RNA-sequencing analysis. Canine CD34+/CD45dim cells exhibited a significantly higher haematopoietic colony formation ability and expressed more similarity in the gene expression profiles to human and mouse HSPCs than those of the other cell fractions. Furthermore, the canine CD34+/CD45dim cells expressed candidate cell surface antigens necessary to define the canine haematopoietic hierarchy roadmap. These results indicate that the canine CD34+/CD45dim cells express the HSPC characteristics more than the other cell fractions, thereby suggesting that these cells have the potential to be used for studying haematopoietic stem cells in dogs.

Quantitative parameter mapping of contrast agent concentration and relaxivity and brain tumor extracellular pH.

In clinical magnetic resonance imaging, gadolinium-based contrast agents are commonly used for detecting brain tumors and evaluating the extent of malignancy. We present a new method to evaluate relaxivity (r1) and contrast agent concentration separately in contrast-enhanced lesions using quantitative parameter mapping (QPM). Furthermore, we also aimed to estimate the extracellular pH (pHe) of tumor lesions. We demonstrated that it is possible to evaluate pathophysiological tumor changes due to therapeutic efficacy by measuring r1 in contrast-enhanced lesions. In this study, the primary brain tumor group showed significantly higher r1 values than other brain disease groups (P < 0.001). Moreover, mean pHe value showed a trend for tumor malignancy having a lower pHe value and primary brain tumor having a significantly lower pHe than other brain diseases (P < 0.001). Our results might suggest that QPM can separately quantify r1 and CA concentration in brain tumors and that pHe brain tumor mapping could serve as a tumor biomarker. In conclusion, our method has potential clinical applications for assessing the treatment effects.